Method for assisting in measuring tumor residue and recurrence

By analyzing ctDNA from peripheral and tumor organ drainage veins to determine mutation abundance ratios, the method enhances the sensitivity and specificity of tumor residual and recurrence detection, improving patient prognosis.

CN119220677APending Publication Date: 2024-12-31AOMING (HANGZHOU) GENE TECH CO LTD
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Patent Information

Application Number
CN202411396307.8
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-10-08
Publication Date
2024-12-31

AI Technical Summary

Technical Problem

Current methods for measuring tumor residual and recurrence in oncology lack sensitivity and specificity, leading to delayed detection of tumor recurrence after imaging indicates residual tumor.

Method used

Collect blood samples from peripheral veins and tumor organ drainage veins during surgery, analyze ctDNA for specific mutations or markers, and calculate the mutation abundance ratio to determine the presence of micro-metastases using molecular biology techniques combined with imaging analysis.

Benefits of technology

Improves the sensitivity and specificity of tumor residual and recurrence monitoring, enhancing patient prognosis and survival by accurately detecting early-stage tumor recurrence.

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Abstract

The invention discloses a method for assisting in measuring tumor residue and recurrence. The method is combined with iconography analysis to determine mutation abundance or a proportion value of other marker content of mutation detected in tumor organ drainage venous blood and peripheral blood of which a medical image does not show that peripheral organ metastasis exists but a mutation level shows that a patient has tiny metastasis; the method is used as a threshold value for auxiliary measurement of tumor residue and recurrence. If the mutation abundance or the concentration of other markers jointly detected in the drainage venous blood and the peripheral blood of the tumor organ is smaller than or equal to a threshold value, auxiliary diagnosis can be carried out on the existence of small tumor metastases in the body of a patient, namely the existence of tumor residues or recurrence. In addition, the other markers include copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens, ctDNA fragmentation patterns.
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Description

Technical Field

[0001] The present invention relates to the field of tumor gene detection, and specifically to a method for using the ratio of ctDNA in peripheral venous blood and drainage venous blood to assist in measuring tumor residual and recurrence. Background Art

[0002] In the field of oncology, tumor residual measurement and recurrence monitoring are crucial to patient prognosis. Currently, the gold standard for measuring tumor residual in clinical practice is through imaging methods. However, due to limited detection sensitivity, once tumor residual is detected by imaging, it may indicate that the tumor has recurred. Therefore, it is very necessary to develop a method with high sensitivity and specificity to assist in tumor residual measurement and recurrence monitoring.

[0003] In view of this, the purpose of the present invention is to provide a method for assisting in measuring tumor residual and recurrence monitoring by examining the ctDNA ratio in peripheral venous blood and drainage venous blood (Chinese invention patent, application number: 202410500662.9, application publication number: CN 118389639 A; a method for detecting free nucleic acids in organ drainage venous blood), so as to improve the sensitivity and specificity of tumor residual measurement and recurrence monitoring, and improve the prognosis and survival of tumor patients. Summary of the invention

[0004] The technical problem to be solved by the present invention is to overcome the shortcomings of existing auxiliary methods for measuring tumor residual and recurrence monitoring, and to provide a method for auxiliary measurement of tumor residual and recurrence that can overcome the above problems or partially solve the above problems, so as to assist in improving the sensitivity and specificity of tumor residual measurement and recurrence monitoring, thereby improving the prognosis and survival of tumor patients.

[0005] In order to achieve the above-mentioned purpose, the technical scheme of the present invention is as follows: the first step is to collect blood samples from the patient's peripheral veins before surgery; the second step is to collect blood samples from the patient's tumor organ drainage veins during surgery; the third step is to extract and analyze ctDNA from the collected patient's peripheral venous blood and tumor organ drainage venous blood respectively; the fourth step is to use molecular biology technology to quantitatively analyze specific mutations or other markers in ctDNA, compare the mutation abundance or other marker content of ctDNA in the tumor organ drainage venous blood and the peripheral venous blood, and calculate the mutation abundance of the common mutations detected in the tumor organ drainage venous blood and the peripheral venous blood. The fifth step is to combine imaging analysis to determine the ratio of the mutation abundance or other marker content of the mutation detected in the tumor organ drainage venous blood and peripheral venous blood, which shows that the patient already has micro-metastases, and use it as an auxiliary measure of the threshold for tumor residual and recurrence. If the mutation abundance or other marker concentration of the mutation detected in the tumor organ drainage venous blood and peripheral venous blood is less than or equal to the threshold, it can assist in diagnosing that the patient already has micro-metastases, that is, there is tumor residual or recurrence. In addition, in most cases, the specific mutations or other markers detected in the tumor organ drainage venous blood and peripheral venous blood come from the same gene because they are all DNA fragments or molecular markers produced by the same tumor cell; if there are significant differences, after excluding the differences in the detection methods, it indicates that the tumor is heterogeneous. At the same time, the other markers include copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens, and ctDNA fragmentation patterns. Compared with the existing auxiliary measurement methods for tumor residual and recurrence monitoring, the auxiliary measurement method for tumor residual and recurrence provided by the present invention can improve the sensitivity and specificity of tumor residual measurement and recurrence monitoring, and improve the prognosis and survival of tumor patients.

[0006] According to the embodiments of the present invention, the present invention can be further optimized, and the following is the technical scheme formed after optimization: In one preferred embodiment, a method for assisting in measuring tumor residual and recurrence, the tumor is colorectal cancer, the colorectal cancer organ drainage vein is the portal vein, the blood collection location of the colorectal cancer organ drainage vein is the portal vein, and the peripheral vein is the peripheral vein of the limb, and the threshold for assisting in measuring colorectal cancer residual and recurrence is determined to be 2 / 3 in combination with imaging analysis, and if the mutation abundance ratio value of the mutations detected jointly from the portal vein blood and the peripheral venous blood is less than or equal to 2 / 3, it indicates that the patient has colorectal cancer residual or colorectal cancer recurrence. The commonly detected mutations are NRAS 61, PIK3CA 545, IDH1 132, PIK3CA 1047, BRAF 600, TP53 175, KRAS 61, KRAS 13, TP53 248, KRAS 12, TP53 273, PIK3CA 542, AKT1 17, GNAS 201, PIK3CA345, PTEN 130, TP53 220, TP53 245, TP53 213, FBXW7 465, PIK3CA 546, ERBB2 310, TP53282, SMAD4 361, TP53 179, KRAS 146, CTNNB1 41, NRAS 12, FBXW7 505, CDKN2A 80, CTNNB145, TP53 176, PIK3CA 88, ERBB3 104, PIK3CA 1043, TP53 163, ERBB2 755, TP53 342, TP53196, BRAF 469, PIK3CA 420, TP53 195, TP53 X187_sice, TP53 266, SF3B1 625, BRAF 594, FBXW7 479, TP53 X307_sice, TP53 173, TP53 238, PPP2R1A 183, TP53 236, TP53 275, TP53 135, TP53 278, PIK3CA111, TP53 241, TP53 237, MAP2K157, TP53 272, ATM 337, TP53 132, ERBB2 678, TP53 215, BRAF 581, BRAF 466, PTEN 233, POLE 286, TP53 242, PIK3CA 344, TP53 X261_sice, MED1244, TP53 274, PIK3CA108、ERBB2 777、TP53 X331_sice、KRAS 60、ERBB2 842、SMAD4537、TP53 306、POLE 411、TP53 286、RAF1 257、KRAS 117、PIK3R1 564、MAP2K1 53、TP53141、SMAD4 386、TP53 126、PIK3CA 1049、PIK3CA 1021、PIK3CA 38、ARID1A 1989、MAX 60、SMAD4 351、PIK3R1 567、MTOR 2215、TGFBR2 553、SMAD2 464、TP53 X33_sice、PTEN 173、TP53 258、ERBB3 232、APC 1429、SMAD4 356、ERBB3 846、FBXW7 658、FBXW7 689、TP53 127、APC 1367、B2M X23_sice、ATM 3008、PTEN 68、FBXW7 367、TCF7L2 471、MAP2K1 128、APC1378、TGFBR1 241、PAX5 26、FBXW7 582、EP300 1466、ATM 250、SMAD4 419、PIK3R1 348、BCL6 594、APC 1397、APC 935、TP53 152、TP53 168、PRKCI 480、APC 1406、APC 1338、SMAD4330、TP53 125、MYC 161、FBXW7 520、APC 1353、FGFR2 203、CTNNB1 383、TP53 257、RHOA37、APC 1408、FBXW7 278、ASXL2 1、KRAS 22、APC 1379、ALK 401、DIS3 689、GLI1 380、APC213、APC 1303、APC 1294、APC 1328、HLA-A 180、NSD1 392、TGFBR1 375、PIK3CB 321、ERRFI1 409、ETV6 369、CDK12 890、MSH2 580、TP53 232、DNMT1 432、RNF43 132、SMAD3268、PRDM14 505、PIK3CA 357、RECQL4 X766_sice、TP53 190、APC 1315、SMAD2 463、SMAD2321、CARD11 423、SMAD2 303、SMAD2 305、SMAD4C363del, SMAD4 G365_E377del, SMAD4D537_E538dup, MED12, K42_N46del, PIK3R1 E458del, PIK3R1 E462_R465del, PIK3R1 D440_K448del, PIK3R1 H450_E451dup, PIK3R1 D578_M582delinsE, PIK3R1 L573del, PIK3R1S399_L404del, TP53 I255del, TP53 L265del, TP53 N235del, TP53 V274_C275dup, TP53C229_H233del, TP53 C238_S240del, TP53 I255dup, TP53 L252dup, TP53 N235_Y236dup, TP53 S269_E271del, TP53 N131del, TP53 V157_R158del, TP53 P177_C182del, TP53 H178_S183del, TP53 G199_E204del, PIK3CA E110del, PIK3CA E110_K111dup, PIK3CA I112_L113del, PIK3CA K111_I112del, PIK3CA, G451_D454del, PIK3CA P449_L456del, PIK3CAG106_R108del, PIK3CA P104_V105del, ERBB2 Y772_A775dup、SOX9 One or more of the mutation sites: K167del, SOX9R152del, CTNNB1 S45del, CTNNB1 Y30_S33del, CTNNB1 S23_S33del, CTNNB1 W25_D32del, MAP2K1 E102_I103del, CREBBP S1680del, HIST1H1C K23del, MTOR W1456_L1460delinsC, MTOR Y1450_W1456del, KIT D579del, KIT V560del, LATS2 P479_A480dup, BRAF T599dup, MYC S298del, U2AF1 G222_G223del, ANKRD11 K1461del.

[0007] In one preferred embodiment, a method for assisting in measuring tumor residual and recurrence, the tumor is an abdominal organ tumor, the organ drainage vein of the abdominal organ tumor is the portal vein or its tributary venous blood, and the peripheral vein is the peripheral vein of the limb. In one preferred embodiment, the abdominal organ tumor is gastric cancer. In one preferred embodiment, the abdominal organ tumor is intestinal cancer. In one preferred embodiment, the abdominal organ tumor is pancreatic cancer. In one preferred embodiment, the abdominal organ tumor is liver cancer. In one preferred embodiment, the abdominal organ tumor is bile duct cancer. In one preferred embodiment, the abdominal organ tumor is a spleen tumor. In one preferred embodiment, the blood collection site of the portal vein or its tributary venous blood is the portal vein. In one preferred embodiment, the blood collection site of the portal vein or its tributary venous blood is the superior mesenteric vein. In one preferred embodiment, the blood collection site of the portal vein or its tributary venous blood is the inferior mesenteric vein. In one preferred embodiment, the blood collection site of the portal vein or its tributary venous blood is the pancreatic vein. In one of the preferred embodiments, the blood collection location of the portal vein or its tributary blood is the splenic vein. In one of the preferred embodiments, the blood collection location of the portal vein or its tributary blood is the subesophageal vein. In one of the preferred embodiments, the blood collection location of the portal vein or its tributary blood is the left gastric vein. In one of the preferred embodiments, the blood collection location of the portal vein or its tributary blood is the right gastric vein. In one of the preferred embodiments, the blood collection location of the portal vein or its tributary blood is the gallbladder vein. In one of the preferred embodiments, the blood collection location of the portal vein or its tributary blood is the paraumbilical vein. In one of the preferred embodiments, the blood collection location of the portal vein or its tributary blood is the duodenal vein. In a preferred embodiment, the mutations detected in the abdominal organ tumor organ drainage venous blood and peripheral venous blood are NRAS 61, KRAS 146, PPP2R1A 183, PIK3CA 344, SMAD4 351, FBXW7 582, PIK3CA 545, CTNNB1 41, TP53 X126_sice, TP53 X261_sice, PIK3R1567, EP300 1466, IDH1 132, NRAS 12, NRAS 13, MED12 44, MTOR 2215, ATM 250, PIK3CA1047, FBXW7 505, TP53 205, TP53 274, TGFBR2 553, SMAD4 419, BRAF 600, CDKN2A 80, PIK3CA 726, PIK3CA 108, SMAD2 464, PIK3R1 348, TP53175、CTNNB1 45、TP53 151、ERBB2777、TP53 X33_sice、BCL6 594、KRAS 61、TP53 176、TP53 236、TP53 X331_sice、PTEN 173、APC 1397、KRAS 13、PIK3CA 88、TP53 275、KRAS 60、TP53 258、APC 935、TP53 248、ERBB3104、TP53 135、ERBB2 842、ERBB3 232、TP53 152、KRAS 12、PIK3CA 1043、TP53 278、SMAD4537、APC 1429、TP53 168、TP53 273、TP53 163、PIK3CA 111、TP53 306、SMAD4 356、PRKCI480、PIK3CA 542、ERBB2 755、TP53 241、POLE 411、ERBB3 846、APC 1406、AKT1 17、TP53342、TP53 237、TP53 286、FBXW7 658、APC 1338、GNAS 201、TP53 196、MAP2K1 57、RAF1257、FBXW7 689、SMAD4 330、PIK3CA 345、BRAF 469、TP53 272、KRAS 117、TP53 127、TP53125、PTEN 130、PIK3CA 420、ATM 337、PIK3R1 564、APC 1367、MYC 161、TP53 220、TP53195、TP53 132、MAP2K1 53、B2M X23_sice、FBXW7 520、TP53 245、TP53 X187_sice、ERBB2678、TP53 141、ATM 3008、APC 1353、TP53 213、TP53 266、TP53 215、SMAD4 386、PTEN 68、FGFR2 203、FBXW7 465、SF3B1 625、BRAF 581、TP53 126、FBXW7 367、CTNNB1 383、PIK3CA546、BRAF 594、BRAF 466、PIK3CA 1049、TCF7L2 471、TP53 257、ERBB2 310、FBXW7 479、PTEN 233、PIK3CA 1021、MAP2K1 128、RHOA 37、TP53 282 TP53 X307_sice、POLE286、PIK3CA 38、APC 1378、APC 1408、SMAD4 361、TP53 173、TP53 242、ARID1A 1989、TGFBR1241、FBXW7 278、TP53 179、TP53 238、PPP2R1A 183、MAX 60、PAX5 26、ASXL2 1、KRAS 22、ETV6 369、SMAD2 321、PIK3R1、 S399_L404del、TP53 H178_S183del、CTNNB1 Y30_S33del、APC 1379、CDK12 890、CARD11 423、TP53 I255del、TP53 G199_E204del、CTNNB1 S23_S33del、ALK 401、MSH2 580、SMAD2 303、TP53 L265del、PIK3CA E110del、CTNNB1 W25_D32del、DIS3 689、TP53 232、SMAD2 305、TP53 N235del、PIK3CA E110_K111dup、MAP2K1E102_I103del、GLI1 380 DNMT1 432、SMAD4 C363del、TP53 V274_C275dup、PIK3CA I112_L113del、CREBBP S1680del、APC 213、RNF43 132、SMAD4 G365_E377del、TP53 C229_H233del、PIK3CA K111_I112del、HIST1H1C K23del、APC 1303、SMAD3 268、SMAD4 D537_E538dup、TP53 C238_S240del、PIK3CA G451_D454del、MTOR W1456_L1460delinsC、APC1294、PRDM14 505、MED12、K42_N46del、TP53 I255dup、PIK3CA P449_L456del 、MTORY1450_W1456del、APC 1328 PIK3CA 357、PIK3R1 E458del、TP53 L252dup、PIK3CA G106_R108del、KIT D579del、HLA-A 180、RECQL4 X766_sice、PIK3R1 E462_R465del、TP53 N235_Y236dup PIK3CA P104_V105del、KITV560del, NSD1 392, TP53 190, PIK3R1 D440_K448del, TP53 S269_E271del, ERBB2 Y772_A775dup, LATS2 P479_A480dup, TGFBR1 375, APC 1315, PIK3R1 H450_E451dup, TP53 N131del, SOX9 K167del, BRAF T599dup, PIK3CB321, SMAD2 463, PIK3R1 D578_M582delinsE, TP53 V157_R158del, SOX9 R152del, MYCS298del, ERRFI1 409, ETV6 369, PIK3R1 L573del, TP53 P177_C182del, CTNNB1 S45del, U2AF1 G222_G223del, ALK-ATIC, ALK-MSN, ALK-TPM4, RET-TRIM27, ROS1-MYO5A, NTRK3-ETV6, ALK-CARS, ALK-NPM1, ALK-TPR, RET-TRIM33, ROS1-PPFIBP1, CD74-NRG1, ALK-CLTCAL K-PPFIBP1, ALK-VCL, ROS1-CD74, ROS1-PWWP2A, NTRK1-LMNA, ALK-DCTN1, ALK-RANBP2, ALK-WDCP, ROS1-CLIP1, ROS1-SDC4, NTRK1-TFG, ALK-EML4, ALK-SEC31A, RET-NCOA4, R One or more of the mutation sites of OS1-ERC1, ROS1-SHTN1, NTRK1-TP53, ALK-FN1, ALK-SQSTM1, RET-PCM1, ROS1-EZR, ROS1-SLC34A2, NTRK1-TPM3, ALK-HIP1, ALK-STRN, RET-PRKAR1A, ROS1-GOPC, ROS1-TPM3, NTRK1-TPR, ALK-KIF5B, ALK-TFG, RET-RELCH, ROS1-HLA-A, ROS1-TPM3, NTRK2-NACC2, ALK-KLC1, ALK-TPM3, RET-TRIM24, ROS1-LRIG3, ROS1-ZCCHC8, and NTRK2-QKI.

[0008] In one preferred embodiment, a method for assisting in measuring tumor residual and recurrence, wherein the tumor is a pelvic organ tumor, the organ drainage vein is the ovarian vein or its tributary venous blood, and the peripheral vein is the peripheral vein of a limb. In one preferred embodiment, the pelvic organ tumor is ovarian cancer. In one preferred embodiment, the pelvic organ tumor is endometrial cancer. In one preferred embodiment, the pelvic organ tumor is uterine fibroids. In one preferred embodiment, the pelvic organ tumor is fallopian tube cancer. In one preferred embodiment, the pelvic organ tumor is peritoneal mesothelioma. In one preferred embodiment, the blood collection location of the ovarian vein or its tributary venous blood is the ovarian vein. In one preferred embodiment, the blood collection location of the ovarian vein or its tributary venous blood is the right ovarian vein. In one preferred embodiment, the blood collection location of the ovarian vein or its tributary venous blood is the left ovarian vein. In one preferred embodiment, the blood collection location of the ovarian vein or its tributary venous blood is the ovarian venous plexus. In one preferred embodiment, the blood collection location of the ovarian vein or its tributary venous blood is the inferior vena cava. In one preferred embodiment, the blood sampling location of the ovarian vein or its tributary venous blood is the left renal vein. In one preferred embodiment, the blood sampling location of the ovarian vein or its tributary venous blood is the internal iliac vein. In a preferred embodiment, the mutations detected in the pelvic organ tumor organ drainage venous blood and peripheral venous blood are NRAS 61, TP53 245, TP53 196, TP53 151, BRAF 581, TP53 M237_N239del, PIK3CA 545, TP53 213, TP53 195, B2M 1, TP53 X261_sice, TP53S260_L264dup, PIK3CA 1047, TP53 282, TP53 X187_sice, TP53 275, TP53 244, TP53 T253_L257del, BRAF 600, TP53 179, TP53 266, TP53 278, FOXL2 134, TP53 T256del, TP53 175, CTNNB1 33, TP53 234, TP53 241, TP53 X331_sice, TP53 A138_L145del, TP53 248, TP53193, TP53 12. TP53176, TP53 238, TP53 157, PIK3R1 I442_N453del, TP53One or more of the mutation sites of D148_T155dup, TP53 273, TP53163, PPP2R1A 183, TP53 272, TP53 G244_M246delinsV, TP53 T155_R156del, TP53 220, TP53 342, TP53 X126_sice, TP53 132, TP53 I254_T256del, TP53 P177_H178del, TP53P191del, ERBB2 Y772_A775dup, CTNNB1 D32_S33del, BRAF-FCHSD1, BRAF-JHDM1D, BRAF-MKRN1, BRAF-AGTRAP, BRAF-GATM, BRAF-RNF130, BRAF-AGK, BRAF-PAPSS1, BRAF-AGAP3, BRAF-AKAP9, BRAF-GNAI1, BRAF-SLC45A3, BRAF-ARMC10, BRAF-PCBP2, BRAF-GTF2I, BRAF-CEP89, BRAF-HERPUD1, BRAF-SND1, BRAF-PJA2, BRAF-PPFIBP2, BRAF-ZNF767, BRAF-CLCN6, BRAF-KIAA1549, BRAF-TRIM24, BRAF-CSTF3, BRAF-SEPT3, RET-TRIM27, BRAF-FAM131B, BRAF-LSM14A, BRAF-ZSCAN30, BRAF-CUL1, BRAF-ZKSCAN1, RET-TRIM33, CD74-NRG1, NTRK1-TPM3, NTRK3-ETV6, RET-HOOK3, RET-PCM1, NTRK1-LMNA, NTRK1-TPR, RET-CCDC6, RET-KIF5B, RET-PRKAR1A, NTRK1-TFG, NTRK2-NACC2, RET-ERC1, RET-KTN1, RET-RELCH, NTRK1-TP53, NTRK2-QKI, RET-GOLGA5, RET-NCOA4, RET-TRIM24.

[0009] In one preferred embodiment, a method for assisting in measuring tumor residual and recurrence, the tumor is a pelvic organ tumor, the organ drainage vein is the uterine vein or its tributary venous blood, and the peripheral vein is the peripheral vein of the limb. In one preferred embodiment, the pelvic organ tumor is endometrial cancer. In one preferred embodiment, the pelvic organ tumor is uterine fibroids. In one preferred embodiment, the pelvic organ tumor is cervical cancer. In one preferred embodiment, the pelvic organ tumor is fallopian tube cancer. In one preferred embodiment, the pelvic organ tumor is ovarian cancer. In one preferred embodiment, the blood collection location of the uterine vein or its tributary venous blood is the uterine vein. In one preferred embodiment, the blood collection location of the uterine vein or its tributary venous blood is the ovarian vein. In one preferred embodiment, the blood collection location of the uterine vein or its tributary venous blood is the vaginal vein. In one preferred embodiment, the blood collection location of the uterine vein or its tributary venous blood is the uterovaginal plexus vein. In one preferred embodiment, the blood collection location of the uterine vein or its tributary venous blood is the internal iliac vein. In a preferred embodiment, the mutations detected in the pelvic organ tumor organ drainage venous blood and peripheral venous blood are NRAS 61, TP53 266, PIK3CA 38, PTEN 129, PIK3R1L449_K459del, PIK3CA E110del, PIK3CA 545, BCOR 1459, ARID1A 1989, DICER1 1810, PIK3R1 L449_Q455del, PIK3CA K111del, PIK3CA 1047, PPP2R1A 179, PPP2R1A 256, PTPRD431, PIK3R1 L466_E469del, PIK3CA L113del, TP53 175, PIK3CA 118, FGFR2 382, DNMT151, PIK3R1, L466_Y470delinsF, PIK3CA E453del, KRAS 61, FBXW7 479, PIK3R1 567, FGFR2375, PIK3R1 N453_Y463del, PIK3CA G463_N465delinsD, KRAS 13, TP53 173, RHEB 35, ARID1A 1722, PIK3R1 Q455_K459del, PIK3CA P449_L452del, TP53 248, TP53 238, RRAS272, PTEN 155, PIK3R1 Q457_E462del, PIK3CA G106_N107del, KRAS12、PPP2R1A 183、PIK3CA 901、PIK3CA 39、PIK3R1 R465_Y467del、PIK3CA I102del、TP53 273 TP53 X126_sice、PTEN X70_sice、TP53 262、PIK3R1 S460_D464del、PIK3CA H419_C420del、PIK3CA542、B2M 1、SOX17 403、SOX17 96、PIK3R1 T576del、PIK3CA W11_P18del、AKT1 17、PIK3CA111、PTEN 136、NF1 461、PIK3R1 R574del、EGFR D770_P772dup、PIK3CA 345、TP53 241、FBXW7 658、PPM1D 525、PIK3R1 K575_R577del、CREBBP S1680del、PTEN 130、TP53 237、CCND1 287、HNF1A 114、PIK3R1 E558_K561del、MTOR A1459_D1468del、TP53 220、FGFR2549、FBXW7 689、TP53 178、PIK3R1 E558_R562del、ESR1 V422del、TP53 245、 ERBB2 678、DICER1 1813、PIK3R1 E451_Y452del、PIK3R1 I566_P568delinsT、ANKRD11 K1461del、TP53213、PTEN 233、CCND1 286、PIK3R1 K459del、PIK3R1 I571_Q572insR、PIK3CA 545、FBXW7465、TP53 239、ARID1A 693、PIK3R1 L449del、PIK3R1 I571_R574del、PIK3CA 1047、PIK3CA546、POLE 286、PTEN 92、PIK3R1 N441_T454del、PIK3R1 K575_R577dup、KRAS 13、CTNNB137、TP53 242、PIK3CA 1025、PIK3R1 E458del、PIK3R1 K575_T576del、KRAS 12、CTNNB1 32、NFE2L2 82、SOS1 233、PIK3R1 K448_N453del、PIK3R1 L570_D578del、PIK3CA 542、TP53179PIK3CA 344、ARID1A 1276、PIK3R1 Q457_S460del、PIK3R1 L570_I571insY、AKT1 17、CTNNB1 33、PIK3CA 93、MAX 28、PIK3R1 D440_E451del、PIK3R1 M563_L570delinsI、PTEN130、NRAS 12、PIK3CA 108、CTCF 377、PIK3R1 D464_E468dup、PIK3R1 P568_L573del、FBXW7465、TP53 193、ERBB2 842、PIK3R1 348、PIK3R1 E451del、PIK3R1 Q579_Y580delinsH、ERBB2 310、FBXW7 505、PIK3CA 106、FUBP1 430、PIK3R1 E462_Y463delinsD、PIK3R1 R577_D578del、CTNNB1 32、U2AF1 34、POLE 411、FBXW7 423、PIK3R1 E462dup、PIK3R1 R577_L581del、FBXW7 505、ESR1 537、FGFR2 252、ACVR1 206、PIK3R1 G446_E451del、PIK3R1I405del、ERBB3 104、PIK3CA 88、ERBB3 297、ARID1A 1335、PIK3R1 H450_E451insD、PIK3R1I405_L420del、FBXW7 479、ERBB3 104、MYCN 44、SPOP 117、PIK3R1 H450_K459del、PIK3R1V401_N406del、MAPK1 322、PIK3CA 1043、NFE2L2 80、CTCF 448、PIK3R1 H450_T454del、TP53 L252del、EP300 1399、ERBB2 755、PIK3CA 1049、PIK3R2 373、PIK3R1 H450del、TP53C277dup、SMO 414、PIK3CA 420、ESR1 536、CTNNB1 35、PIK3R1 I442_E443delinsK、TP53Y236_M237delinsL、HGF 229、CTNNB1 34、PIK3CA 1021、PTEN 127、PIK3R1 K448_Y452del、TP53 P128_L130del、TGFBR1259, one or more of the following mutation sites: CDKN2A V28_E33del, PIK3R1 D569_L581delinsE, PIK3R1 Y580_L581insF, TP53 G199_E204del, CD74-NRG1, FGFR2-TACC3, PET-CCDC6, MET-CAV1, NTRK1-TFG, FGFR2-CLIP1, FGFR2-LZTFL1, FGFR2-TNS1, RET-ERC1, MET-CAV2, NTRK1-TP53, FGFR2-DBP, FGFR2-MGEA5, FGFR2-TRIM55, RET-GOLGA5, MET-CAV3, NTRK1-TPM3, FGFR2-DDX21, FGFR2-NRAP, FGFR2-TRIM8, RET-HOOK3, MET-CAV4, NTRK1-TPR, FGFR2-ERC1, FGFR2-NRBF2, FGFR2-TTC28, RET-KIF5B, MET-CAV5, NTRK3-ETV6, FGFR2-FAM76A, FGFR2-OPTN, FGFR2-USP33, RET-KTN1, MET-CAV6, FGFR2-AHCYL1, FGFR2-FILIP1, FGFR2-PAWR, FGFR2-WAC, RET-NCOA4, MET-CAV7, FGFR2-ATAD2, FGFR2-G3BP2, FGFR2-PDHX, FGFR2-WDHD1, RET-PCM1, MET-CAV8, FGFR2-ATE1, FGFR2-HOOK1, FGFR2-POC1B, FGFR2-ZMYM4, RET-PRKAR1A, MET-CAV9, FGFR2-BICC1, FGFR2-INA, FGFR2-PPHLN1, FGFR3-BAIAP2L1, RET-RELCH, MET-CAV10, FGFR2-CCDC147, FGFR2-KCTD1, FGFR2-ROCK1, FGFR3-ELAVL3, RET-TRIM24, MET-CAV11, FGFR2-CCDC170, FGFR2-KIAA1217, FGFR2-SORBS1, FGFR3-RGS12, RET-TRIM27, MET-CAV12, FGFR2-CCDC6, FGFR2-KIAA1598, FGFR2-SYNPO2, FGFR3-TACC3, RET-TRIM33, MET-CAV13, FGFR2-CIT, FGFR2-KIAA1967, FGFR2-TACC2, FGFR3-IGH

[0010] In one preferred embodiment, a method for assisting in measuring tumor residual and recurrence, wherein the tumor is a tumor of the breast, chest wall or other chest structure, the organ drainage vein is the breast vein or its tributary venous blood, and the peripheral vein is the peripheral vein of the limb. In one preferred embodiment, the breast, chest wall or other chest structure tumor is breast cancer. In one preferred embodiment, the breast, chest wall or other chest structure tumor is a chest wall tumor. In one preferred embodiment, the breast, chest wall and other chest structure tumor is lung cancer. In one preferred embodiment, the blood collection location of the breast vein or its tributary venous blood is the vein of the breast. In one preferred embodiment, the blood collection location of the breast vein or its tributary venous blood is the superficial vein of the breast. In one preferred embodiment, the blood collection location of the breast vein or its tributary venous blood is the deep vein of the breast. In one preferred embodiment, the blood collection location of the breast vein or its tributary venous blood is the perforator of the internal thoracic vein. In one preferred embodiment, the blood collection location of the breast vein or its tributary venous blood is the tributary of the axillary vein. In one preferred embodiment, the blood collection location of the breast vein or its tributary venous blood is the intercostal vein. In a preferred embodiment, the mutations detected in the venous blood draining the tumor organs of the breast, chest wall and other chest structures and in the peripheral venous blood are PIK3CA 545, TP53 195, TP53 274, FGFR4 550, TP53 133, TP53 I255del, PIK3CA1047, CDKN2A 83, XPO1 571, PIK3CA 104, RAD51C 21, TP53 N239_S240del, TP53 175, TP53X187_sice, ERBB2 777, CDH1 X278_sice, HIST1H1C 115, TP53 G245_P250delinsA, TP53248, TP53 266, TP53 X331_sice, AKT1 52, FOXA1 C258_R261del, TP53 R156del, KRAS 12, TP53 249, TP53 306, CTCF 226, FOXA1 G284_G290del, TP53 C141_P142del, TP53 273, TP53234, CDH1 23, ERBB2 869 FOXA1 K264_K267del, TP53 D148_T150del, PIK3CA 542, PIK3CA 118, TP53 286, CTCF 284, FOXA1 K267dup, TP53 I162_Y163delinsN, AKT117、TP53X307_sice、ERBB3 928、PTEN 126、FOXA1 N252_G257del、TP53 L130_A138dup、PIK3CA 345、TP53 173、TP53 X225_sice、PTEN 124、FOXA1 N397_F400del、TP53 P153_G154del、PTEN130、TP53 238、TP53 141、FOXA1 250、MED12 N46_S52del、TP53 P177_C182del、TP53 220、PPP2R1A 183、TP53 216、FOXA1 242、MED12 P49_E55del、TP53 S183_G187delinsC、TP53245、TP53 X126_sice、TP53 337、TP53 113、MED12 V41_S52del、PIK3CA E110del、TP53213、TP53 205、TP53 126、FGFR4 535、PIK3R1 F456_Q457del、PIK3CA K111del、PIK3CA546、PIK3CA 726、 PIK3CA 1049、MAP3K1 380、PIK3R1 E462_R465del、PIK3CA E453_P466del、ERBB2 310、TP53 151、ESR1 536、 CDH1 X722_sice、PIK3R1 K448_N453del、PIK3CA L452_G460del、SMAD4 361、TP53 236、TP53 255、CDH1 335、PIK3R1 N453del、PIK3CA L452_P458del、TP53 179、TP53 135、TP53 194、GATA3 364、PIK3R1 Q455_F456insL、PIK3CA G106_R108del、SF3B1 700、TP53 278、PIK3CA 1044、MAP2K4 184、PIK3R1 E468_E469insGEYDRLYE、PIK3CA I102_E103delinsK、TP53 193、PIK3CA 111、PIK3CA 81、FOXA1 226、PIK3R1 E468_E469insGLYE、PIK3CA R108del、ESR1 538、TP53 241、ESR1 380、FOXP1 X511_sice、PIK3R1N453_Q455delinsK, PIK3CA H419_C420del, ESR1537, FGFR2 549, ERBB3 329, MAP2K4 X297_sice, PIK3R1 R465dup, ERBB2 Y772_A775dup, TP53 176, TP53 157, TP53 270, IGF1R 129, PIK3R1 Y452_N453insF, ERBB2 G778_P780dup, PIK3CA 88, TP53 272, GATA3 293, TP53 208, PIK3R1, K567_L570del, CTNNB1 S45del, ERBB3104, TP53 132 HIST1H1C 180, GATA3 366、PIK3R1 R574del、HIST1H1C K23del、PIK3CA1043、PIK3CA 453、ERBB2 769、TP53 10、PIK3R1 K567del、KIT M552_Y570del、TP53 163、TP53 280、PTEN X70_sice、CDH1 63、PIK3R1 D569dup、LATS2 P479_A480dup、ERBB2 755、RHOA 17、NUP93 14、CBFB 1、PIK3R1 I571_L581del、NFE2L2 E79del、TP53 342、TP53 239、FOXA1 176、CTCF 288、PIK3R1 K567_I571del、ESR1 V422del、TP53 196、TP53 242、TP53136、CBFB 73、PIK3R1 V402_L413del、AKT2 C60_I75dup、PIK3CA 420、TP53 X261_sice、FOXA1 247、TBX3 113、PIK3R1 L380del、AKT2 R67_L78dup、AKT1P68_C77dup, NTRK1-LMNA, RET-CCDC6, RET-PRKAR1A, UNK-ABCA5, ALK-KIF5B, ALK-STRN, NTRK1-TFG, RET-ERC1, RET-RELCH, ALK-ATIC, ALK-KLC1, ALK -TFG, NTRK1-TP53, RET-GOLGA5, RET-TRIM24, ALK-CARS, ALK-MSN, ALK-TPM3, NTRK1-TPM3, RET-HOOK3, RET-TRIM27, ALK-CLTC, ALK-NPM1, ALK-TPM4, N One or more of the mutation sites of TRK1-TPR, RET-KIF5B, RET-TRIM33, ALK-DCTN1, ALK-PPFIBP1, ALK-TPR, NTRK2-NACC2, RET-KTN1, BCAS4–BCAS3, ALK-EML4, ALK-RANBP2, ALK-VCL, NTRK2-QKI, RET-NCOA4, ARFGEF2-SULF2, ALK-FN1, ALK-SEC31A, ALK-WDCP, NTRK3-ETV6, RET-PCM1, ABCA5-PPP4R1L, ALK-HIP1, and ALK-SQSTM1.

[0011] In one preferred embodiment, a method for assisting in measuring tumor residual and recurrence, the tumor is an organ tumor of the urinary system and endocrine system, the organ drainage vein is the renal vein or its tributary venous blood, and the peripheral vein is the peripheral vein of the limb. In one preferred embodiment, the organ tumor of the urinary system and endocrine system is renal cell carcinoma. In one preferred embodiment, the organ tumor of the urinary system and endocrine system is renal pelvic cancer. In one preferred embodiment, the organ tumor of the urinary system and endocrine system is adrenocortical carcinoma. In one preferred embodiment, the organ tumor of the urinary system and endocrine system is pheochromocytoma. In one preferred embodiment, the organ tumor of the urinary system and endocrine system is ureteral cancer. In one preferred embodiment, the blood collection location of the renal vein or its tributary venous blood is the renal vein. In one preferred embodiment, the blood collection location of the renal vein or its tributary venous blood is the right renal vein. In one preferred embodiment, the blood collection location of the renal vein or its tributary venous blood is the left renal vein. In one preferred embodiment, the blood collection location of the renal vein or its tributary venous blood is the left adrenal vein. In one of the preferred embodiments, the blood collection location of the renal vein or its tributary blood is the interlobular vein. In one of the preferred embodiments, the blood collection location of the renal vein or its tributary blood is the perinephric vascular plexus. In one of the preferred embodiments, the blood collection location of the renal vein or its tributary blood is the adrenal vein. In one of the preferred embodiments, the blood collection location of the renal vein or its tributary blood is the subcapsular venous plexus of the stellate vein. In one of the preferred embodiments, the blood collection location of the renal vein or its tributary blood is the perinephric vein. In one of the preferred embodiments, the blood collection location of the renal vein or its tributary blood is the arcuate vein. In one of the preferred embodiments, the blood collection location of the renal vein or its tributary blood is the interlobar vein. In one of the preferred embodiments, the blood collection location of the renal vein or its tributary blood is the lobar vein. In one of the preferred embodiments, the blood collection location of the renal vein or its tributary blood is the renal segmental vein. In a preferred embodiment, the mutations detected in the venous blood and peripheral venous blood of organ tumors of the urinary system and endocrine system are PIK3CA 545, MTOR 2215, MET 1250, VHL68, KMT2D 1375, PIK3R1 I571_K575del, PIK3CA 1047, RHEB 35, VHL 111, VHL 158, VHL114, MTOR E1455_D1458dup, KRAS 12, MTOR 1977, MTOR 1888, VHL 86, EGFR 838, MTORE1455_E1457dup, TP53273,PIK3CB 1067,MTOR 2427,VHL 74,VHL 115,LATS2 P479_A480dup,PIK3CA 542,VHL X114_sice,VHL 78,MTOR 1483,MTOR 1460,AKT2 R76_I84dup,TP53 213,VHL 65.PBRM1 1160,MTOR 2006,KDM6A 526,VHL F76del,TP53 135,VHL X155_sice,EP300 X1429_sice,VHL 161,MET 1094,VHL I75_C77del,NFE2L2 29,VHL 89. MET1200, GSK3B X239_sice, PBRM1 X856_sice, VHL R79_S80del, NFE2L2 81, GNAQ 96, MET1230, VHL 151, VHL 169, TCEB1 79, VHL 80, VHL 121, STK11 174, VHL 135, SDHAF2 X87_sice, MET 1070, VHL 88, VHL 162, BAP1 E31del, EGFR-PURB, EGFR-HMGA2, MET-CD47, MET-EPHB4, MET-DST, MET-STARD3NL, EGFR-RAD51, EGFR-SEPT1 4. MET-CCDC6, MET-CLIP2, MET-KIF5B, MET-ST7, RET-TRIM33, CD74-NRG1, NTRK1-TPM3, NTRK3-ETV6, RET-HOO K3, RET-PCM1, NTRK1-LMNA, NTRK1-TPR, RET-CCDC6, RET-KIF5B, RET-PRKAR1A, NTRK1-TFG, NTRK2-NACC2, RET-ERC1, RET-KTN1, RET-RELCH, NTRK1-TP53, NTRK2-QKI, RET-GOLGA5, RET-NCOA4, RET-TRIM24 mutation sites.

[0012] In one preferred embodiment, a method for assisting in measuring tumor residual and recurrence, the tumor is an organ tumor of the central nervous system, the organ drainage vein is the cerebral vein or its tributary venous blood, and the peripheral vein is the peripheral vein of the limb. In one preferred embodiment, the organ tumor of the central nervous system is a glioma. In one preferred embodiment, the organ tumor of the central nervous system is a meningioma. In one preferred embodiment, the organ tumor of the central nervous system is a medulloblastoma. In one preferred embodiment, the organ tumor of the central nervous system is a pituitary adenoma. In one preferred embodiment, the organ tumor of the central nervous system is a spinal cord tumor. In one preferred embodiment, the organ tumor of the central nervous system is a brain metastasis. In one preferred embodiment, the blood collection location of the cerebral vein or its tributary venous blood is the superficial cerebral vein. In one preferred embodiment, the blood collection location of the cerebral vein or its tributary venous blood is the superior cerebral vein. In one preferred embodiment, the blood collection location of the cerebral vein or its tributary venous blood is the middle superficial cerebral vein. In one preferred embodiment, the blood collection location of the cerebral vein or its tributary venous blood is the inferior cerebral vein. In one of the preferred embodiments, the blood collection location of the cerebral vein or its tributary venous blood is the deep cerebral vein. In one of the preferred embodiments, the blood collection location of the cerebral vein or its tributary venous blood is the internal cerebral vein. In one of the preferred embodiments, the blood collection location of the cerebral vein or its tributary venous blood is the basal vein. In one of the preferred embodiments, the blood collection location of the cerebral vein or its tributary venous blood is the great cerebral vein. In one of the preferred embodiments, the blood collection location of the cerebral vein or its tributary venous blood is the medullary vein. In one of the preferred embodiments, the blood collection location of the cerebral vein or its tributary venous blood is the vein of the diencephalon. In one of the preferred embodiments, the blood collection location of the cerebral vein or its tributary venous blood is the vein of the brainstem. In one of the preferred embodiments, the blood collection location of the cerebral vein or its tributary venous blood is the vein of the cerebellum. In one of the preferred embodiments, the blood collection location of the cerebral vein or its tributary venous blood is the dural sinus. In a preferred embodiment, the mutations detected in the central nervous system organ tumor organ drainage venous blood and peripheral venous blood are NRAS 61, TP53 195, PIK3R1 376, CIC 231, PIK3R1 D440del, TP53 S269_E271delinsK, PIK3CA 545, TP53 266, MAX 60, ALK 1245, PIK3R1 D464_Y470dup, TP53 T231_I232insTDCTT, IDH1 132, TP53 249, H3F3A 35, PTENX342_sice、PIK3R1 E439del、TP53 N131del、PIK3CA 1047、TP53234、CIC 202、PDGFRA 659、PIK3R1 E458_Y463dup、TP53 A161_I162del、BRAF 600、PIK3CA118、PIK3R1 X582_sice、CIC 205、PIK3R1 E468_Y470dup、TP53 P128del、TP53 175、TP53X307_sice、EGFR 222、PIK3R1 379、PIK3R1 F456_K459del、TP53 P142dup、TP53 248、TP53173、EGFR 252、PIK3R1 560、PIK3R1 G446_L449delinsV、TP53 P153del、KRAS 12、TP53238、FGFR1 687、PTPN11 308、PIK3R1 H450_E451del、TP53 T155_R158del、TP53 273、TP53205、TP53 246、PTPN11 285、PIK3R1 H450_Q455dup、TP53 H179del、PIK3CA 542、EGFR 598、PTEN 132、CIC 238、PIK3R1 L449_H450insQ、TP53 P191del、PIK3CA 345、TP53 158、SMARCA4 1192、PTEN 71、PIK3R1 L466del、PIK3CA E110del、PTEN 130、TP53 236、 CIC1512、 SMO 535、PIK3R1 N453_D464dup、PIK3CA E453del、TP53 220、TP53 275、PTPN11 76、ATRX X199_sice、PIK3R1 N453_Q457del、PIK3CA E453_T462del、TP53 245、PIK3CA 111、ACVR1 328、TP53 120、PIK3R1 Q455_S460dup、PIK3CA H450_L455del、TP53 213、TP53 237、CIC 1515、PTPN11 507、PIK3R1 Y463_E468dup、PIK3CA L436_P449dup、FBXW7 465、TP53132、TP53 136、PTPN11 61、PIK3R1 T576del、PIK3CAL455_G460delinsF、PIK3CA 546、CIC215、EGFR 62、PTPN11 461、PIK3R1 K567_L570del、PIK3CA L10_M16del、TP53 282、PIK3CA453、ACVR1 258、ATRX 907、PIK3R1 K567del、EGFR N771_H773dup、CTNNB1 37、CDKN2A 110、PTPN11 510、CIC 203、PIK3R1 K575_L581delinsM、EGFR A767_V769dup、CTNNB1 32、TP53244、TP53 130、PDGFRA 235 、PIK3R1 M563_N564delinsI、EGFR H773dup、TP53 179、ALK1275、PIK3CA 1、SMARCA4 K546del、PIK3R1 N564_P568delinsT、EGFR S768_D770dup、CTNNB1 33、ALK 1174、SMARCA4 781、BAP1 Y33del、 PIK3R1 E403_L404del、 EGFR H773_V774dup、TP53 193、SMARCA4 910、 PTPN11 69、SMARCB1 K364del、PIK3R1 E403_L404delinsV、EGFR Y764_D770dup、IDH2 172、 HIST1H3B 28、SMO 412、PIK3R1 E451_Y452del、PIK3R1 T397_V401del、NOTCH1 F357del、EGFR 289、FGFR1 577、EGFR 304、PIK3R1D464_Y467del、PIK3R1 V401_H407del、NOTCH1 S356del、PIK3CA 88、EGFR 108、EGFR 363、PIK3R1 F456_Q457del、PIK3R1 L380del、NOTCH1 C359del、PIK3CA 1043、PIK3R1 564、EGFR596、 PIK3R1 K459del、PIK3R1 K379del、NOTCH1 Y358del、TP53 163、TP53 281、ATRX1426、PIK3R1 L449del、PIK3R1 N378del、NOTCH1 D338del、TP53 196、TP53 216、CIC201, PIK3R1 N441_T454del, TP53 I255del, CREBBP S1680del, H3F3A 28, PTPN11 72, PDGFRA229, PIK3R1 Q455_F456insL, TP53 L265del, PIK3CA 420, MYCN 44, TP53 155, PIK3R1R461_E462delinsQ, TP53 N239_S241del, CTNNB1 34, PDGFRA 842, EGFR 263, PIK3R1Y452dup, TP53 C275_R282delinsW, One or more of the mutation sites RET-PRKAR1A, EGFR-PURB, NTRK1-LMNA, NTRK1-TPR, RET-CCDC6, RET-KIF5B, RET-RELCH, EGFR-RAD51, NTRK1-TFG, NTRK2-NACC2, RET-ERC1, RET-KTN1, RET-TRIM24, EGFR-SEPT14, NTRK1-TP53, NTRK2-QKI, RET-GOLGA5, RET-NCOA4, RET-TRIM27, EGFR-HMGA2, NTRK1-TPM3, NTRK3-ETV6, RET-HOOK3, RET-PCM1, and RET-TRIM33.

[0013] In one preferred embodiment, a method for assisting in measuring tumor residual and recurrence, the tumor is an organ tumor of the urinary system, the organ drainage vein is the bladder vein and its tributary venous blood, and the peripheral vein is the peripheral vein of the limb. In one preferred embodiment, the organ tumor of the urinary system is bladder cancer. In one preferred embodiment, the organ tumor of the urinary system is adenocarcinoma. In one preferred embodiment, the organ tumor of the urinary system is squamous cell carcinoma. In one preferred embodiment, the organ tumor of the urinary system is prostate cancer. In one preferred embodiment, the organ tumor of the urinary system is cervical cancer with tumor infiltration of the bladder. In one preferred embodiment, the organ tumor of the urinary system is uterine corpus cancer when the tumor spreads to the bladder. In one preferred embodiment, the organ tumor of the urinary system is a rectal tumor that affects the bladder through local infiltration. In one preferred embodiment, the organ tumor of the urinary system is a pelvic tumor that infiltrates or metastasizes to the bladder. In one preferred embodiment, the blood collection location of the bladder vein and its tributary venous blood is the bladder vein. In one preferred embodiment, the blood collection location of the bladder vein and its tributary venous blood is the prostate vein. In one of the preferred embodiments, the blood collection location of the bladder vein and its tributary venous blood is the uterine vein. In one of the preferred embodiments, the blood collection location of the bladder vein and its tributary venous blood is the bladder venous plexus. In one of the preferred embodiments, the blood collection location of the bladder vein and its tributary venous blood is the internal iliac vein. In one of the preferred embodiments, the blood collection location of the bladder vein and its tributary venous blood is the inguinal vein. In a preferred embodiment, the mutations commonly detected in the organ drainage venous blood and peripheral venous blood of organ tumors of the urinary system are NRAS 61, CTNNB1 33, FGFR2 549, ERBB4 707, KDM6A 1336_sice LYN 364, PIK3CA 545, TP53 193, RXRA 427, RB1 X405_sice, ERCC2 246, AXL 443, PIK3CA 1047, FBXW7 505, NFE2L2 34, FGFR3 370, BRAF 485 KMT2A 1264, BRAF 600, U2AF1 34, PIK3CA453, FGFR3 650, EP300 1164, RAD51C 224, TP53 175, CDKN2A 80, TP53 280, HIST1H1C 180, MAP2K1 386, SPRED1 349, KRAS 61, CTNNB1 45, GTF2I 440, ERBB3 228, FBXW7532、KDM6AX76_sice、KRAS 13、ERBB3 104、ERBB2 678、ERCC2 484、ERCC2 14、KDM6A X129_sice、TP53248、ERBB2 755、CREBBP 1446、HRAS 117、FOXP1 514、KDM6A 1003、KRAS 12、FGFR3 373、ERBB4 1289、KDM6A 555、ERCC2 463、TNFRSF14 111、TP53 273、HRAS 13、ERCC2 238、FGFR3380、KMT2D 1903、CDKN2A N39_N42del、PIK3CA 542、CDKN2A 83、MAPK1 322、ERCC2 24、ERCC2 609、SMAD4 V539_A546del、AKT1 17、BRAF 594、TP53 285、STAG2 216、ERCC2 606、MED12 G44_F45del、FGFR3 249、TP53 234、TP53 214、FGFR3 371、JUN 112、TP53 R158_A159dup、HRAS 61、FBXW7 479、PIK3CA 106、CDK6 65、SESN2 425、PIK3CA W11_H14delinsY、TP53 220、TP53 X307_sice、MAP2K1 53、RHOA 161、ERBB2 660、ERBB2 Y772_A775dup、TP53245、TP53 238、ERBB3 297、ERBB3 332、NCOA3 80、EGFR N771_H773dup、TP53 213、 PIK3CA726、NUP93 15、ERBB3 91、ERBB2 103、EGFR D770_N771insGF、FBXW7 465、TP53 151、SF3B1902、TP53 161、AXL 273、EGFR P772_H773ins、TPNP、PIK3CA 546、HRAS 12、TP53 159、ERCC272、ERBB2 277、CREBBP S1680del、ERBB2 310、FGFR3 248、ERBB3 329、RHOA 47、ERBB3 103、LATS2 P479_A480dup、TP53 282、TP53 278、CDKN2A 108、TP53 271、EP300One or more of the mutation sites of 1455, NFE2L2L30_S33del, CTNNB1 37, TP53 241, TP53 258, ASXL2 330, FBXW7 546, U2AF1 G223del, FGFR2-AHCYL1, FGFR2-FAM76A, FGFR2-NRBF2, FGFR2-TRIM55, NTRK1-LMNA, RET-KIF5B, FGFR2-ATAD2, FGFR2-FILIP1, FGFR2-OPTN, FGFR2-TRIM8, NTRK1-TFG, RET-KTN1, FGFR2-ATE1, FGFR2-G3BP2, FGFR2-PAWR, FGFR2-TTC28, NTRK1-TP53, RET-NCOA4, FGFR2-BICC1, FGFR2-HOOK1, FGFR2-PDHX, FGFR2-USP33, NTRK1-TPM3, RET-PCM1, FGFR2-CCDC147, FGFR2-INA, FGFR2-POC1B, FGFR2-WAC, NTRK1-TPR, RET-PRKAR1A, FGFR2-CCDC170, FGFR2-KCTD1, FGFR2-PPHLN1, FGFR2-WDHD1, NTRK2-NACC2, RET-RELCH, FGFR2-CCDC6, FGFR2-KIAA1217, FGFR2-ROCK1, FGFR2-ZMYM4, NTRK2-QKI, RET-TRIM24, FGFR2-CIT, FGFR2-KIAA1598, FGFR2-SORBS1, FGFR3-BAIAP2L1, NTRK3-ETV6, RET-TRIM27, FGFR2-CLIP1, FGFR2-KIAA1967, FGFR2-SYNPO2, FGFR3-ELAVL3, RET-CCDC6, RET-TRIM33, FGFR2-DBP, FGFR2-LZTFL1, FGFR2-TACC2, FGFR3-RGS12, RET-ERC1, CD74-NRG1, FGFR2-DDX21, FGFR2-MGEA5, FGFR2-TACC3, FGFR3-TACC3, RET-GOLGA5, FGFR2-ERC1, FGFR2-NRAP, FGFR2-TNS1, FGFR3-IGH, RET-HOOK3.

[0014] In one preferred embodiment, a method for assisting in measuring tumor residual and recurrence, the tumor is an organ tumor of the liver and its adjacent organs and systems, the organ drainage vein is the hepatic vein or its tributary venous blood, and the peripheral vein is the peripheral vein of the limb. In one preferred embodiment, the organ tumor of the liver and its adjacent organs and systems is hepatocellular carcinoma. In one preferred embodiment, the organ tumor of the liver and its adjacent organs and systems is intrahepatic bile duct carcinoma. In one preferred embodiment, the organ tumor of the liver and its adjacent organs and systems is hepatic hemangioma. In one preferred embodiment, the organ tumor of the liver and its adjacent organs and systems is hilar bile duct carcinoma when the tumor invades the liver parenchyma. In one preferred embodiment, the organ tumor of the liver and its adjacent organs and systems is a liver metastasis of colorectal cancer transferred to the liver through the portal vein system. In one preferred embodiment, the organ tumor of the liver and its adjacent organs and systems is a liver metastasis of pancreatic cancer transferred to the liver through the portal vein system. In one preferred embodiment, the organ tumor of the liver and its adjacent organs and systems is a liver metastasis of gastric cancer transferred to the liver. In one preferred embodiment, the organ tumor of the liver and its adjacent organs and systems is a liver metastasis of breast cancer transferred to the liver. In one of the preferred embodiments, the organ tumor of the liver and its adjacent organs and systems is a liver metastasis from lung cancer to the liver. In one of the preferred embodiments, the organ tumor of the liver and its adjacent organs and systems is a pancreatic tail tumor that invades the liver and its venous system. In one of the preferred embodiments, the organ tumor of the liver and its adjacent organs and systems is a gastric cancer that directly spreads and affects the liver. In one of the preferred embodiments, the organ tumor of the liver and its adjacent organs and systems is a hepatic angiosarcoma. In one of the preferred embodiments, the blood collection location of the venous blood of the hepatic vein or its branches is the hepatic vein. In one of the preferred embodiments, the blood collection location of the venous blood of the hepatic vein or its branches is the right hepatic vein. In one of the preferred embodiments, the blood collection location of the venous blood of the hepatic vein or its branches is the middle hepatic vein. In one of the preferred embodiments, the blood collection location of the venous blood of the hepatic vein or its branches is the left hepatic vein. In one of the preferred embodiments, the blood collection location of the venous blood of the hepatic vein or its branches is the inferior vena cava. In a preferred embodiment, the mutations detected in the organ drainage venous blood and peripheral venous blood of organ tumors of the liver and its adjacent organs and systems are IDH1 132, CTNNB1 41, CTNNB1 335, JAK1 910, TP53 V157_R158dup, CTNNB1 L31_S33del, PIK3CA 1047, TP53 193, CTNNB1 387, GPS2 X242_sice, MDC1I1020_R1028del、CTNNB1Q28_D32delinsH、GNAS 201、CTNNB1 45、CDKN2A X51_sice、AXIN1 X652_sice、CTNNB1 A43_P44dup、CTNNB1 T42_K49del、TP53 220、TP53 163、CTNNB1 36、ERRFI1 116、CTNNB1 D32_I35delinsV、CTNNB1 W25_H36del、CTNNB1 37、CTNNB1 34、SF3B1 741、FH 336、CTNNB1 D32_S37delinsA、NFE2L2 W24_D29delinsY、CTNNB1 32、TP53 249、STAT3 410、CDKN1A 1、CTNNB1G34_S71del、NFE2L2 Q73_T80del、CTNNB1 33、NFE2L2 82、CTNNB1 35、PIK3R1 R574del、CTNNB1One or more of the mutation sites of L31_I35del, FGFR1-PLAG1, FGFR1-FGFR1OP, FGFR2-ERC1, FGFR2-OPTN, FGFR2-USP33, RET-GOLGA5, FGFR1-TACC1, FGFR1-ZMYM2, FGFR2-FAM76A, FGFR2-PAWR, FGFR2-WAC, RET-HOOK3, FGFR1-ZNF703, FGFR1-ZNF198, FGFR2-FILIP1, FGFR2-PDHX, FGFR2-WDHD1, RET-KIF5B, FGFR1-BAG4, FGFR2-AHCYL1, FGFR2-G3BP2, FGFR2-POC1B, FGFR2-ZMYM4, RET-KTN1, FGFR1-BCR, FGFR2-ATAD2, FGFR2-HOOK1, FGFR2-PPHLN1, NTRK1-LMNA, RET-NCOA4, FGFR1-CEP110, FGFR2-ATE1, FGFR2-INA, FGFR2-ROCK1, NTRK1-TFG, RET-PCM1, FGFR1-CNTRL, FGFR2-BICC1, FGFR2-KCTD1, FGFR2-SORBS1, NTRK1-TP53, RET-PRKAR1A, FGFR1-CUX1, FGFR2-CCDC147, FGFR2-KIAA1217, FGFR2-SYNPO2, NTRK1-TPM3, RET-RELCH, FGFR1-ERLIN2, FGFR2-CCDC170, FGFR2-KIAA1598, FGFR2-TACC2, NTRK1-TPR, RET-TRIM24, FGFR1-ACVR1, FGFR2-CCDC6, FGFR2-KIAA1967, FGFR2-TACC3, NTRK2-NACC2, RET-TRIM27, FGFR1-EBF2, FGFR2-CIT, FGFR2-LZTFL1, FGFR2-TNS1, NTRK2-QKI, RET-TRIM33, FGFR1-MITF, FGFR2-CLIP1, FGFR2-MGEA5, FGFR2-TRIM55, NTRK3-ETV6, CD74-NRG1, FGFR1-PDE4DIP, FGFR2-DBP, FGFR2-NRAP, FGFR2-TRIM8, RET-CCDC6, FGFR1-WHSC1L1, FGFR2-DDX21, FGFR2-NRBF2, FGFR2-TTC28, RET-ERC1.

[0015] In one preferred embodiment, a method for assisting in measuring tumor residual and recurrence, the tumor is an organ tumor of the lung and bronchial system, the organ drainage vein is the pulmonary vein or its tributary venous blood, and the peripheral vein is the peripheral vein of the limb. In one preferred embodiment, the organ tumor of the lung and bronchial system is lung cancer. In one preferred embodiment, the organ tumor of the lung and bronchial system is secondary lung cancer formed by breast cancer metastasis to the lung. In one preferred embodiment, the organ tumor of the lung and bronchial system is secondary lung cancer metastasis to the lung from renal cancer. In one preferred embodiment, the organ tumor of the lung and bronchial system is secondary lung cancer metastasis to the lung from colorectal cancer. In one preferred embodiment, the organ tumor of the lung and bronchial system is pulmonary arteriovenous malformation. In one preferred embodiment, the organ tumor of the lung and bronchial system is pulmonary angiosarcoma. In one preferred embodiment, the organ tumor of the lung and bronchial system is bronchial adenoma. In one preferred embodiment, the organ tumor of the lung and bronchial system is bronchial carcinoma. In one of the preferred embodiments, the organ tumor of the lung and bronchial system is a heart-related tumor that affects or uses the pulmonary vein for blood drainage. In one of the preferred embodiments, the organ tumor of the lung and bronchial system is an atrial myxoma that anatomically invades the pulmonary vein. In one of the preferred embodiments, the organ tumor of the lung and bronchial system is a left atrial sarcoma that invades the opening of the pulmonary vein. In one of the preferred embodiments, the organ tumor of the lung and bronchial system is a pleural and mediastinal tumor. In one of the preferred embodiments, the organ tumor of the lung and bronchial system is a pleural mesothelioma that invades the lung and its vascular system, thereby affecting the drainage of the pulmonary vein. In one of the preferred embodiments, the organ tumor of the lung and bronchial system is a mediastinal tumor that invades the lung and the related venous system. In one of the preferred embodiments, the blood collection location of the pulmonary vein or its tributary venous blood is the pulmonary vein. In one of the preferred embodiments, the blood collection location of the pulmonary vein or its tributary venous blood is the left pulmonary vein. In one of the preferred embodiments, the blood collection location of the pulmonary vein or its tributary venous blood is the right pulmonary vein. In one of the preferred embodiments, the blood sampling location of the pulmonary vein or its tributary venous blood is the right upper pulmonary vein. In one of the preferred embodiments, the blood sampling location of the pulmonary vein or its tributary venous blood is the right lower pulmonary vein. In one of the preferred embodiments, the blood sampling location of the pulmonary vein or its tributary venous blood is the left upper pulmonary vein. Preferably, in one of the preferred embodiments, the blood sampling location of the pulmonary vein or its tributary venous blood is the left lower pulmonary vein. In one of the preferred embodiments, the mutations commonly detected in the organ drainage venous blood and peripheral venous blood of organ tumors of the lung and bronchial system are PIK3CA 545, CTNNB134、TP53 X331_sice、MYC 74、FGFR3 8、EGFR L747_T751del、IDH1 132、TP53 195、 TP53 285、EP300 1414、RBM10 X91_sice、EGFR L747_P753delinsS、PIK3CA 1047、CDKN2A 83、TP53 214、RB1 X474_sice、STK11 251、EGFR E746_T751delinsA、BRAF 600、TP53 X187_sice、TP53 286、STK11 X307_sice、KEAP1 320、EGFRL747_E749del、EGFR 858、TP53 266、RAF1 257、TP53 267、STK11 308、EGFR S752_I759del、TP53 175、TP53 249、NFE2L2 31、TP53 164、KEAP1 601、EGFR L747_S752del、KRAS 61、BRAF601、NFE2L2 81、STK11 216、TRAF7 189、EGFR K745_E746insVPVAIK、KRAS 13、BRAF 594、TP53 X225_sice、TP53 144、CDKN2A V28_E33del、EGFR K754_I759del、TP53 248、TP53234、TP53 281、TP53 105、CDKN2A A36_N39delinsD、EGFR T751_A755del、KRAS 12、BCOR1459、TP53 X125_sice、STK11 242、CDKN2A E27del、EGFR T751_E758del、NRAS 61、HRAS13、NFE2L2 29、TP53 154、STK11 239、EGFR E746_A750del、TP53 273、FBXW7 479、TP53337、RB1 X445_sice、PIK3R1 E451_Y452del、EGFR N771_H773dup、PIK3CA 542、TP53 X307_sice、EGFR 768、STK11 220、PIK3R1 D464_Y467del、EGFR A767_V769dup、AKT1 17、TP53173、NFE2L2 80、NOTCH1 853、 PIK3R1 Y452_Q457del、EGFR H773dup、GNAS 201、TP53238、TP53 159、RB1 X127_sice、PIK3R1 Y467_Y470del、EGFR S768_D770dup、FGFR3 249、TP53 X126_sice、TP53 194、SF3B1 740、PIK3R1 K567_L570del、EGFR D770、_N771insG、PIK3CA 345、 TP53 205、TP53 X224_sice、TP53 172、PIK3R1 R577del、EGFR D770_N771insGL、PTEN 130、PIK3CA 726、MET 1010、ERBB2 659、 TP53 E286_E287del、EGFRD770_N771insY、HRAS 61、TP53 158、SMAD4 351、TP53 155、TP53 N235del、EGFR N771_P772insH、TP53 220、TP53 236、CDKN2A 108、STK11 X288_sice、TP53 S241dup、EGFR N771_P772insHH、TP53 245、B2M 1、CDKN2A 84、GATA2 352、TP53 T256_S260del、EGFR N771_P772insV、TP53 213、TP53 275、TP53 270、TP53 331、TP53 C238_M243del、EGFR P772_H773dup、FBXW7 465、TP53 135、RRAS2 72、BRAF 596、TP53 D281_R282insP、EGFR E709_T710delinsD、ERBB2 310、TP53 278、TP53 258、STK11 X97_sice、TP53 E285_K292del、CTNNB1 S45del、TP53 282、TP53 241、RB1 X405_sice、KEAP1 470、TP53 L252_I254del、CTNNB1 S33_A39del、CTNNB1 37、EGFR 719、TP53 134、KRAS 11、TP53 L264_N268del、MAP2K1 E102_I103del、CTNNB1 32、TP53 237、SMARCA4 1232、TP53 131、TP53 N263_N268del、CREBBP S1680del、SMAD4361、NFE2L2 34、HIST1H1C 180、EGFR 750、TP53 P250_L252del、KIT D579del、TP53 179、TP53 157、STK11 223、STK11 181、TP53 R282_R283del、LATS2 P479_A480dup、CTNNB1 33、MAP2K1 57、STK11 X155_sice、DNMT3B 229、TP53 T231_I232del、LATS2 P479_A480insPP、KRAS 146、TP53 272、STK11 X245_sice、RAD50 69、TP53V272_R273insL、NFE2L2 D21_I22delinsE、CTNNB1 41、TP53 132、TP53 246、RB1 X89_sice、TP53 N131del、NFE2L2 D27del、EGFR 790、TP53 280、TP53 110、IL7R 241、TP53 R156del、NFE2L2 E35_R42del、TP53 193、NFE2L2 79、STK11 194、KEAP1 480、TP53 C135_L137delinsW、NFE2L2 F37del、FBXW7 505、TP53 215、EGFR 747、KEAP1 110、TP53 G154_T155del、NFE2L2 G31del、U2AF1 34、MET X1010_sice、EGFR 709、KEAP1 272、TP53I162dup、NFE2L2 I22_D29del、CDKN2A 80、BRAF 581、TP53 277、STK11 165、TP53 L130del、NFE2L2 R34_F37delinsL、CTNNB1 45、CDK4 24、GNAS 227、DIS3 479、TP53 Q136_C141del、NFE2L2 S33_R34del、TP53 176、BRAF 466、NFE2L2 24、EGFR 754、TP53 T150_R158del、NFE2L2 L74_Q87del、TP53 163、TP53 239、TP53 298、HIST1H3B 106、TP53 P177_C182del、BRAF T599dup、ERBB2 755、TP53 242、EGFR 62、EGFR 833、TP53P191del、BRAF V600_R603del、TP53 342、TP53 X261_sice、NFE2L2 26、KEAP1 333、TP53 P191_L201del、DAXXE457del、TP53 196、EGFR 861、DIS3 488、KEAP1 417、PIK3CA E110del、STAT3 E616del、BRAF 469、TP53 244、SOS1 233、MET 1003、ERBB2 Y772_A775dup、PIK3CA 420、TP53 274、ARAF 214、KEAP1 155、ERBB2G778_P780dup, ALK-MSN, ALK-ATIC, NTRK1-LMNA, ALK-TPM4, MET-CAV1, MET-EPHB4, ALK-NPM1, ALK-CARS, NTRK1-TFG, and ALK -TPR, MET-CCDC6, MET-HLA-DRB1, ALK-PPFIBP1, ALK-CLTC, NTRK1-TP53, ALK-VCL, MET-CD47, MET-KIF5B, ALK-RANBP2, ALK -DCTN1、NTRK1-TPM3、ALK-WDCP、MET-CD74、MET-DST、ALK-SEC31A、ALK-EML4、NTRK1-TPR、EGFR-PURB、MET-CLIP2、MET-PT PRZ1, ALK-SQSTM1, ALK-FN1, NTRK2-NACC2, EGFR-RAD51, MET-STARD3NL, MET-ST7, ALK-STRN, ALK-HIP1, NTRK2-QKI, EGFR-2. SEPT14, ALK-TPM3, ALK-KLC1, ALK-TFG, ALK-KIF5B, NTRK3-ETV6, EGFR-HMGA2, RET-TRIM33, ROS1-EZR, RET-CCDC6, RET-H OOK3, RET-NCOA4, RET-RELCH, ROS1-CD74, ROS1-GOPC, RET-ERC1RET-KIF5B, RET-PCM1, RET-TRIM24, ROS1-CLIP1, ROS1-HL A-A, RET-GOLGA5, RET-KTN1, RET-PRKAR1A, RET-TRIM27, ROS1-ERC1, ROS1-LRIG3, ROS1-MYO5A, ROS1-PWWP2A, ROS1-SHTN 1, ROS1-TPM3, ROS1-ZCCHC8, EZR-ERBB4, ROS1-PPFIBP1, ROS 1-SDC4, ROS1-SLC34A2, ROS1-TPM3, and CD74-NRG1.

[0016] In one preferred embodiment, a method for assisting in measuring tumor residual and recurrence, the tumor is an organ tumor of the esophagus and adjacent organs, the organ drainage vein is the esophageal vein or its tributary venous blood, and the peripheral vein is the peripheral vein of the limb. In one preferred embodiment, the organ tumor of the esophagus and adjacent organs is esophageal cancer. In one preferred embodiment, the organ tumor of the esophagus and adjacent organs is a tumor at the gastroesophageal junction. In one preferred embodiment, the organ tumor of the esophagus and adjacent organs is a tumor at the gastric cardia. In one preferred embodiment, the organ tumor of the esophagus and adjacent organs is a mediastinal tumor. In one preferred embodiment, the organ tumor of the esophagus and adjacent organs is a mediastinal lymphoma. In one preferred embodiment, the organ tumor of the esophagus and adjacent organs is a thymic tumor. In one preferred embodiment, the organ tumor of the esophagus and adjacent organs is a lung cancer invading the esophagus. In one preferred embodiment, the organ tumor of the esophagus and adjacent organs is a bronchial carcinoma invading the mediastinum and esophageal region. In one of the preferred embodiments, the organ tumor of the esophagus and adjacent organs is liver cancer under portal hypertension. In one of the preferred embodiments, the organ tumor of the esophagus and adjacent organs is liver metastasis under portal hypertension. In one of the preferred embodiments, the organ tumor of the esophagus and adjacent organs is pancreatic cancer under portal hypertension. In one of the preferred embodiments, the organ tumor of the esophagus and adjacent organs is colorectal cancer under portal hypertension. In one of the preferred embodiments, the blood collection location of the esophageal vein or its tributary venous blood is the esophageal vein. In one of the preferred embodiments, the blood collection location of the esophageal vein or its tributary venous blood is the inferior thyroid vein. In one of the preferred embodiments, the blood collection location of the esophageal vein or its tributary venous blood is the azygos vein. In one of the preferred embodiments, the blood collection location of the esophageal vein or its tributary venous blood is the hemiazygos vein. In one of the preferred embodiments, the blood collection location of the esophageal vein or its tributary venous blood is the accessory hemiazygos vein. In one of the preferred embodiments, the blood collection location of the esophageal vein or its tributary venous blood is the gastric coronary vein. In a preferred embodiment, the mutations commonly detected in the organ drainage venous blood and peripheral venous blood of organ tumors of the esophagus and adjacent organs are PIK3CA 545, TP53 176, TP53 272, ERBB2 769, ERBB4 1002, TP53 T253dup, PIK3CA 1047, PIK3CA 88, GTF2I 440, SMAD4 356, ERBB4 1223, TP53 C238_N239delinsY, TP53 175, ERBB3 104, NFE2L2 79, ERBB3 846, RHOA 22 TP53P250_I251delinsL、KRAS 61、TP53 163、ERBB2 678、TP53 91、HNF1A 591、TP53 S240_C242del、KRAS 13、ERBB2 755、TP53 215、PARP1 500、INPPL1 70、TP53 S240_S241del、TP53 248、TP53 342、TP53 X261_sice、CDH1 254、CTNNB1535、TP53 N131del、KRAS 12、TP53 196、TP53 244、RHOA 5、PLK2 208、TP53 V157_R158del、TP53 273、TP53 195、PIK3CA 93、TP53 317, PIK3CD 894, TP53 Q136del, PIK3CA 542, CDKN2A 83, RHOA 42, PAX5 26, ERBB4 1102, TP53 V147_D148dup, AKT1 17, TP53 X187_sice, ERBB2 777, SMARCA4 781, ERBB4 774, TP53 P177_C182del, GNAS 201, TP53 266, TP53285, FBXW7 545, MAP3K13 X502_sice, TP53 H178_S183del, PIK3CA 345, TP53 249, TP53306, ERBB4 798, CDH1 190, TP53 C176dup, TP53 220, TP53 234, TP53 214, IL7R 395, CDKN2A V28_E33del, TP53 H179_D184del, TP53 245, FBXW7 479, SMARCA4 910, PTPN11503, CDKN2A L32_L37del, TP53 P191del, TP53 213, TP53 X307_sice, TP53 286, ARID1A2087, CDKN2A G35_A36del, TP53 V197_N200del, FBXW7 465, TP53 173, NFE2L2 31, KNSTRN12, SMAD4 R361_G365del, PIK3CA E453_D454del, PIK3CA 546、TP53 238、NFE2L2 81、TP53294、SMAD4 F362_H371del、ERBB2 M774dup、ERBB2 310、TP53X126_sice、ERBB3 297、PREX250、SMAD4 R361_L364del、 MDC1 K1025del、TP53 282、TP53 205、EP300 1399、RHOA 34、SMAD4 L536_E538delinsQ、SOX9 R152_K167del、CTNNB1 37、TP53 151、SMAD4 386、RHOA57、SMAD4 L540del、CTNNB1 T41_S47del、CTNNB1 32、CDKN2A 58、TP53 X125_sice、CDH1X177_sice、SMARCB1、 K364del、CREBBP S1680del、SMAD4 361、B2M 1、TP53 X224_sice、CDH1 X440_sice、PIK3R1 E451_Y452del、LATS2 P479_A480dup、TP53 179、TP53 275、FGFR2 382、ERBB2 776、PIK3R1 H450_E451insVH、 NFE2L2 I28dup、CTNNB1 33、TP53 135、SMAD4 351、RNF43 86 PIK3R1 R577del、NFE2L2 R34_S40del、KRAS 146、TP53 278、CDKN2A84、PTPRT 668、TP53 I255del、ANKRD11 K1012del、TP53 193、PIK3CA 111、SMAD2 464、RHOA62、TP53 L265del、STAT3 E616del、FBXW7 505、TP53 241、SMARCB1 377、TP53 198、TP53N239_S240del、FGFR2-AHCYL1、FGFR2-CLIP1、FGFR2-INA、FGFR2-NRBF2、 FGFR2-SYNPO2、FGFR2-WAC、FGFR2-ATAD2、FGFR2-DBP、FGFR2-KCTD1、FGFR2-OPTN、FGFR2-TACC2、FGFR2-WDHD1、FGFR2-ATE1、FGFR2-DDX21、FGFR2-KIAA1217、FGFR2-PAWR、FGFR2-TACC3One or several of the mutation sites of FGFR2-ZMYM4, FGFR2-BICC1, FGFR2-ERC1, FGFR2-KIAA1598, FGFR2-PDHX, FGFR2-TNS1, RET-RELCH, FGFR2-CCDC147, FGFR2-FAM76A, FGFR2-KIAA1967, FGFR2-POC1B, FGFR2-TRIM55, RET-TRIM24, FGFR2-CCDC170, FGFR2-FILIP1, FGFR2-LZTFL1, FGFR2-PPHLN1, FGFR2-TRIM8, RET-TRIM27, FGFR2-CCDC6, FGFR2-G3BP2, FGFR2-MGEA5, FGFR2-ROCK1, FGFR2-TTC28, RET-TRIM33, FGFR2-CIT, FGFR2-HOOK1, FGFR2-NRAP, FGFR2-SORBS1, FGFR2-USP33, CD74-NRG1, NTRK1-TP53, NTRK2-NACC2, RET-CCDC6, RET-HOOK3, RET-NCOA4, NTRK1-LMNA, NTRK1-TPM3, NTRK2-QKI, RET-ERC1, RET-KIF5B, RET-PCM1, NTRK1-TFG, NTRK1-TPR, NTRK3-ETV6, RET-GOLGA5, RET-KTN1, RET-PRKAR1A, NRAS 61, CDKN2A 80, TP53 237, TP53 134, CDH1 288, and TP53S241dup.

[0017] In one preferred embodiment, a method for assisting in measuring tumor residual and recurrence, the tumor is an organ tumor of the prostate and adjacent organs, the organ drainage vein is the prostate vein or its tributary venous blood, and the peripheral vein is the peripheral vein of the limb. In one preferred embodiment, the organ tumor of the prostate and adjacent organs is prostate cancer. In one preferred embodiment, the organ tumor of the prostate and adjacent organs is a bladder tumor of the bladder neck and trigone. In one preferred embodiment, the organ tumor of the prostate and adjacent organs is rectal cancer of the lower rectum. In one preferred embodiment, the organ tumor of the prostate and adjacent organs is rectal cancer invading the prostate area. In one preferred embodiment, the organ tumor of the prostate and adjacent organs is a seminal vesicle. In one preferred embodiment, the organ tumor of the prostate and adjacent organs is uterine cancer. In one preferred embodiment, the organ tumor of the prostate and adjacent organs is uterine cancer with prostate cancer-like changes. In one preferred embodiment, the organ tumor of the prostate and adjacent organs is ovarian cancer. In one preferred embodiment, the organ tumor of the prostate and adjacent organs is a soft tissue tumor in the pelvic cavity. In one of the preferred embodiments, the organ tumor of the prostate and adjacent organs is a rhabdomyosarcoma in the pelvic cavity. In one of the preferred embodiments, the organ tumor of the prostate and adjacent organs is a liposarcoma in the pelvic cavity. In one of the preferred embodiments, the blood collection location of the prostatic vein or its tributary venous blood is the prostatic vein. In one of the preferred embodiments, the blood collection location of the prostatic vein or its tributary venous blood is the prostatic venous plexus. In one of the preferred embodiments, the blood collection location of the prostatic vein or its tributary venous blood is the deep dorsal vein of the penis. In one of the preferred embodiments, the blood collection location of the prostatic vein or its tributary venous blood is the bladder venous plexus. In one of the preferred embodiments, the blood collection location of the prostatic vein or its tributary venous blood is the internal iliac vein or its tributaries. In a preferred embodiment, the mutations commonly detected in the organ drainage venous blood and peripheral venous blood of organ tumors of the prostate and adjacent organs are PIK3CA 545, PIK3CA 546, MED12 1224, FOXA1 226, FOXA1, M253_N256del, TP53 L252del, IDH1 132, TP53 282, SPOP 102, FOXA1 219, FOXA1 M253_Y259del, TP53 D148del, PIK3CA 1047, CTNNB1 37, FOXA1 266, HNF1A 338, FOXA1 N252_C258del, TP53 C176_H179del, TP53 175, CTNNB1 32, SPOP131、SPOP 129、 FOXA1 N252_S408del、TP53 E204_L206del、KRAS 61、TP53 179、SPOP 87、FOXA1 F254_N256delinsY、FOXA1 Q263_C268del、TP53 I195_G199del、TP53 248、CTNNB1 33、PIK3R1 X582_sice、FOXA1 E255_N256del、FOXA1 Q263_D296delinsH、PIK3CA N114del、KRAS 12、CTNNB1 41、AR742、FOXA1 G251_F254del、FOXA1 Q263_G281del、PIK3CA H419_L422del、TP53 273、CTNNB145、ERG 354、 FOXA1 G251_G257del、FOXA1 Q263del、CTNNB1 Q26_D32delinsH、PIK3CA542、TP53 176、FOXA1 247、FOXA1 S250_Y259del、FOXA1 R265_K270del、LATS2 P479_A480dup、AKT1 17、BRAF 601、FOXA1 253、FOXA1 A323_P326del、FOXA1 S250_F254del、BRAFK601_W604del、PIK3CA 345、PPP2R1A 183、FOXA1 261、FOXA1 D249_F254del、FOXA1 S250_N252del、BRAF N486_A489delinsK、PTEN 130、SPOP 133、ATM 2875、FOXA1 D249_N252del、FOXA1 S282_G283dup、MYC S298del、HRAS 61、AR 702、SUZ12 101、FOXA1 F254_E255del、FOXA1 S409del、AKT2、L78_Q79insHANTFVIRCL、TP53 220、TP53 215、SPOP 125、FOXA1 、F254_G257delinsC、 PIK3R1 K567_L570del、TP53 245、AR 878、CUL3 299、FOXA1 F254_L260del、PIK3R1 D569_L570delinsV、TP53 213、AR 875、MED12 1223、 FOXA1K264dup,PIK3R1 L573_K575del, FGFR2-TTC28, FGFR1-PLAG1, FGFR1-MITF, FGFR2-CCDC170, FGFR2-INA, FGFR2-PDHX, FGFR2-U SP33, FGFR1-TACC1, FGFR1-PDE4DIP, FGFR2-CCDC6, FGFR2-KCTD1, FGFR2-POC1B, FGFR2-WAC, FGFR1-ZNF703, FGFR1-WHSC1L1, FGFR2-CIT, FGFR2-KIAA1217, FGFR2-PPHLN1, FGFR2-WDHD1, FGFR1-BAG4, FGFR1-FGFR1OP, FGFR2-CLIP1 , FGFR2-KIAA1598, FGFR2-ROCK1, FGFR2-ZMYM4, FGFR1-BCR, FGFR1-ZMYM2, FGFR2-DBP, FGFR2-KIAA1967, FGFR2-SORBS1, FGFR3-BAIAP2L1, FGFR1-CEP110, FGFR1-ZNF198, FGFR2-DDX21, FGFR2-LZTFL1, FGFR2-SYNPO2, FGFR3-ELAVL3, FGFR1-CNTRL, FGFR2-AHCYL1, FGFR2-ERC1, FGFR2-MGEA5, FGFR2-TACC2, FGFR3-RGS12, FGFR1-CUX1 , FGFR2-ATAD2, FGFR2-FAM76A, FGFR2-NRAP, FGFR2-TACC3, FGFR3-TACC3, FGFR1-ERLIN2, FGFR2-ATE1, FGFR2-FILIP1, FGFR2-NRBF2, FGFR2-TNS1, One or more of the mutation sites FGFR3-IGH, FGFR1-ACVR1, FGFR2-BICC1, FGFR2-G3BP2, FGFR2-OPTN, FGFR2-TRIM55, TMPRSS2-ERG, FGFR1-EBF2, FGFR2-CCDC147, FGFR2-HOOK1, FGFR2-PAWR, FGFR2-TRIM8, and BCL2L14-ETV6.

[0018] In one preferred embodiment, a method for assisting in measuring tumor residual and recurrence, the threshold for assisting in measuring tumor residual and recurrence is the ratio of mutation abundance of mutations detected in tumor organ drainage venous blood and peripheral venous blood when medical imaging determines that there is no peripheral organ metastasis, but the patient already has micrometastasis at the mutation level. In one preferred embodiment, the threshold for assisting in measuring tumor residual and recurrence is the ratio of copy number variation detected in tumor organ drainage venous blood and peripheral venous blood when medical imaging determines that there is no peripheral organ metastasis, but the patient already has micrometastasis at the mutation level. In one preferred embodiment, the threshold for assisting in measuring tumor residual and recurrence is the ratio of DNA methylation concentration of DNA methylation detected in tumor organ drainage venous blood and peripheral venous blood when medical imaging determines that there is no peripheral organ metastasis, but the patient already has micrometastasis at the mutation level. In one preferred embodiment, the threshold value for assisting in measuring tumor residual and recurrence is the ratio of the concentration of gene rearrangement fragments detected in the tumor organ drainage venous blood and peripheral venous blood when the medical image determines that there is no peripheral organ metastasis, but the mutation level shows that the patient has micrometastasis. In one preferred embodiment, the threshold value for assisting in measuring tumor residual and recurrence is the ratio of the detection rate of microsatellite instability detected in the tumor organ drainage venous blood and peripheral venous blood when the medical image determines that there is no peripheral organ metastasis, but the mutation level shows that the patient has micrometastasis. In one preferred embodiment, the threshold value for assisting in measuring tumor residual and recurrence is the ratio of the relative abundance or signal intensity of histone modifications detected in the tumor organ drainage venous blood and peripheral venous blood when the medical image determines that there is no peripheral organ metastasis, but the mutation level shows that the patient has micrometastasis. In one preferred embodiment, the threshold value for assisting in measuring tumor residual and recurrence is the relative abundance or signal intensity ratio of chromatin structural changes detected in the tumor organ drainage venous blood and peripheral venous blood when medical imaging confirms that there is no peripheral organ metastasis but the patient has micrometastasis at the mutation level. In one preferred embodiment, the threshold value for assisting in measuring tumor residual and recurrence is the ratio of tumor neoantigen concentration detected in the tumor organ drainage venous blood and peripheral venous blood when medical imaging confirms that there is no peripheral organ metastasis but the patient has micrometastasis at the mutation level.In one preferred embodiment, the threshold value for assisting in measuring tumor residual and recurrence is the characteristic intensity or frequency ratio value of the ctDNA fragmentation pattern detected in the tumor organ drainage venous blood and peripheral venous blood when the medical image confirms that there is no peripheral organ metastasis but the mutation level shows that the patient has micro-metastasis. All the above thresholds are determined by statistical methods, and the p value is less than 0.05.

[0019] In one of the preferred embodiments, a method for assisting in measuring tumor residual and recurrence, the threshold value for assisting in measuring tumor residual and recurrence is a value less than 1. In one of the preferred embodiments, the threshold value is 0.99. In one of the preferred embodiments, the threshold value is 0.98. In one of the preferred embodiments, the threshold value is 0.97. In one of the preferred embodiments, the threshold value is 0.96. In one of the preferred embodiments, the threshold value is 0.95. In one of the preferred embodiments, the threshold value is 0.94. In one of the preferred embodiments, the threshold value is 0.93. In one of the preferred embodiments, the threshold value is 0.92. In one of the preferred embodiments, the threshold value is 0.91. In one of the preferred embodiments, the threshold value is 0.90. In one of the preferred embodiments, the threshold value is 0.89. In one of the preferred embodiments, the threshold value is 0.85-0.88. In one of the preferred embodiments, the threshold value is 0.84-0.8. In one of the preferred embodiments, the threshold value is 0.79-0.75. In one of the preferred embodiments, the threshold value is 0.74-0.70. In one of the preferred embodiments, the threshold value is 0.69-0.65. In one of the preferred embodiments, the threshold value is 0.64-0.6. In one of the preferred embodiments, the threshold value is 0.59-0.55. In one of the preferred embodiments, the threshold value is 0.54-0.5. In one of the preferred embodiments, the threshold value is 0.49-0.45. In one of the preferred embodiments, the threshold value is 0.44-0.4. In one of the preferred embodiments, the threshold value is 0.39-0.35. In one of the preferred embodiments, the threshold value is 0.34-0.3. In one of the preferred embodiments, the threshold value is 0.29-0.25. In one of the preferred embodiments, the threshold value is 0.24-0.2. In one of the preferred embodiments, the threshold value is 0.19-0.15. In one of the preferred embodiments, the threshold value is 0.14-0.1. In one of the preferred embodiments, the threshold value is 0.09-0.05. In one of the preferred embodiments, the threshold value is 0.04-0.

[0020] In one preferred embodiment, a method for assisting in measuring tumor residual and recurrence, the molecular biology technology is digital PCR, qPCR, NGS (next generation sequencing), BEAMing (Beads, Emulsion, Amplification, and Magnetics), ARMS-PCR (Amplification Refractory Mutation System PCR), ddPCR (Droplet Digital PCR), CAPP-Seq (Cancer Personalized Profiling by Deep Sequencing), SHERLOCK (Specific High-sensitivity Enzymatic Reporter Unlocking), MassARRAY, LAMP (Loop-mediated Isothermal Amplification), Sanger sequencing, or a combination of several of them.

[0021] In one preferred embodiment, a method for assisting in measuring tumor residual and recurrence comprises the following steps: a first step, collecting blood samples from the patient's peripheral veins and tumor organ drainage veins, respectively, to extract and analyze ctDNA; a second step, using molecular biology techniques to quantitatively analyze specific mutations or other markers in ctDNA; a third step, comparing the mutation abundance or other marker content of ctDNA in the tumor organ drainage venous blood and the peripheral venous blood, and calculating the ratio of the mutation abundance or other marker content of the mutations detected in the drainage venous blood and the peripheral venous blood; a fourth step, combining imaging analysis to determine the ratio of the mutation abundance or other marker content of the mutations detected in the organ drainage venous blood and the peripheral venous blood, where medical imaging does not show the presence of peripheral organ metastases but the patient already has micrometastases at the mutation level, and using it as a threshold for assisting in measuring tumor residual and recurrence. If the mutation abundance ratio value of the mutations detected in the organ drainage venous blood and the peripheral venous blood or the content ratio value of the other markers is less than or equal to the threshold, it can assist in diagnosing the presence of tumor micrometastases in the patient, that is, the presence of tumor residual or recurrence.

[0022] In one preferred embodiment, a method for assisting in measuring tumor residual and recurrence provides a device for assisting in measuring tumor residual and recurrence, comprising: (1) a data acquisition module for quantitatively analyzing specific mutations or other markers in ctDNA, obtaining quantitative data of specific mutations or other markers in ctDNA and performing quality control; (2) a comparison module for determining specific mutations or other markers commonly detected in ctDNA of tumor organ drainage venous blood and peripheral venous blood; (3) an analysis module for determining the mutation abundance of specific mutations commonly detected in ctDNA of tumor organ drainage venous blood and peripheral venous blood or the content ratio value of other markers; (4) a reporting module for giving a conclusion for assisting in measuring tumor residual and recurrence. If the mutation abundance ratio value of specific mutations commonly detected in ctDNA of tumor organ drainage venous blood and peripheral venous blood or the content ratio value of other markers is ≤ a threshold value, it indicates that there are already tumor micrometastases in the patient's body, that is, there is tumor residual or there is recurrence.

[0023] In one of the preferred embodiments, a method for assisting in measuring tumor residual and recurrence is provided, wherein a computer-readable storage medium is provided, wherein the computer-readable storage medium includes a program that can be executed by a processor to implement the above-mentioned method for assisting in measuring tumor residual and recurrence.

[0024] In one of the preferred embodiments, a method for assisting in measuring tumor residual and recurrence is provided, the method providing the above-mentioned device, the use of the above-mentioned storage medium in preparing the device, and the use of the device to assist in measuring tumor residual and recurrence, assist in guiding targeted drug use, assist in cancer treatment monitoring, and assist in cancer prognosis assessment.

[0025] In one preferred embodiment, a method for assisting in measuring tumor residual and recurrence provides a use of a specific mutation in ctDNA, other markers, or a combination thereof in the preparation of tumor prevention and treatment drugs and / or the preparation of tumor detection reagents.

[0026] Compared with the prior art, the present invention has the following beneficial effects: (1) It fills the technical gap in China and abroad in using mutations or other markers detected in organ drainage venous blood and peripheral venous blood to assist in measuring tumor residual and recurrence; (2) It provides oncology clinicians with a highly sensitive and specific technical tool to assist in measuring residual tumors and recurrence in patients; (3) It provides an auxiliary method to improve the prognosis of cancer patients. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1Schematic diagram of the basic situation of the cohort in Example 1, taking colorectal cancer as an example.

[0028] Figure 2 The p-value table of the cohort in Example 1 was obtained by chi-square test, taking colorectal cancer as an example.

[0029] Figure 3 Schematic diagram of the grouping of the cohort of Example 1 based on the difference in mutation abundance of intraoperative portal vein blood and preoperative peripheral venous blood in mutation detection tissue, taking colorectal cancer as an example.

[0030] Figure 4 Figure 3 Specific data table of differential grouping, taking colorectal cancer as an example.

[0031] Figure 5 Schematic diagram of the development route of the present invention's technology for measuring tumor residual and recurrence, taking colorectal cancer as an example.

[0032] Figure 6 right Figure 3 KEGG analysis results table of the common mutation abundance detected in portal vein blood during surgery / the common mutation abundance detected in peripheral venous blood before surgery ≥ 2 / 3, taking colorectal cancer as an example. DETAILED DESCRIPTION

[0033] The present invention will be described in detail below with reference to the accompanying drawings and in combination with the embodiments. It should be noted that, in the absence of conflict, the embodiments of the present invention and the features in the embodiments can be combined with each other. The embodiments of the present invention are only for explaining the present invention, not for limiting the present invention, and the embodiments of the present invention are not limited to the embodiments given in the specification. The specific experimental conditions or operating conditions not specified in the embodiments are made under conventional conditions, or made under the conditions recommended by the material supplier. In addition, it should be understood that one or more method steps mentioned in the present invention do not exclude that there may be other method steps before and after the combination step or other method steps may be inserted between these explicitly mentioned steps, unless otherwise specified; it should also be understood that the combination connection relationship mentioned in the present invention does not exclude that there may be other connections before and after the combination or other connections may be inserted between these explicitly mentioned two connections, unless otherwise specified. Moreover, unless otherwise specified, the numbering of each method step is only a convenient tool for identifying each method step, rather than for limiting the order of arrangement of each method step or limiting the scope of the present invention. The change or adjustment of its relative relationship, without substantial change in the technical content, should also be regarded as the scope of the present invention. In the following examples, the reagents, materials and instruments used can be commercially available without special instructions.

[0034] The term "draining vein" is also called "draining vein", which is a general term for the venous channels that receive organs or the part of the organ where the tumor is located. "Draining venous blood" refers to the venous blood in the drainage vein, which is the venous blood that flows out of the organ or the part of the organ where the tumor is located but has not yet passed through the next organ tissue.

[0035] The term "blood sampling from drainage veins" refers to the collection of blood from drainage veins, from veins flowing out of organs or the part of an organ where the tumor is located. The blood collected is venous blood that flows out of one organ tissue but has not yet passed through the next organ tissue, thereby minimizing the effects of blood dilution effect, organ metabolism effect, and blood self-degradation effect on the indicators to be tested. Blood sampling from drainage veins is a technically demanding operation that requires experienced doctors or nurses to perform. For patients with abdominal organ tumors, since venous blood from different organs is usually not mixed evenly when it flows into the portal vein and its tributary veins, it is necessary to determine the blood sampling site on the portal vein and its tributary veins according to the direction of the tributary veins or through imaging analysis of the blood flow direction, as well as the depth and direction of the needle insertion to ensure that the needle position can collect tumor venous blood. At the same time, when determining the location of the portal vein and its tributary veins for blood sampling, it is necessary to consider the convenience and safety of the operation, and to minimize the dilution of venous blood from tumors by venous blood from other tissues. This helps to improve the purity and accuracy of the sampling. In addition, it is also necessary to ensure that tumor venous blood can be effectively collected before entering the liver to avoid the liver's metabolic effects on tumor free nucleic acids. Therefore, in the process of collecting portal vein and its tributary venous blood, it is necessary to comprehensively consider factors such as the direction of tumor venous blood flow, anatomical structure, imaging analysis and ease of operation, as well as the purity of tumor-derived venous blood, to ensure accurate acquisition of portal vein and its tributary venous blood samples with as high a proportion of venous blood returning from the tumor as possible. In actual applications, it is also necessary to determine the best method and process based on the patient's specific situation and the doctor's judgment.

[0036] Example 1 Clinical application of peripheral venous blood before colorectal cancer surgery and portal venous blood during surgery The first step was sample collection: 108 different patients were enrolled in the study for preoperative peripheral venous blood and intraoperative portal venous blood, which were centrifuged and platelet removed to separate plasma for ctDNA detection; the second step was to review clinical information: 12 patient samples with poor matching were deleted; the third step was to further review clinical information: 12 patient samples with AJCC stage 4 and its paired samples were deleted; the fourth step was to construct a new nested case-control cohort, including 42 patients in the case group and 42 patients in the control group, as shown in the attached figure. Figure 1 and attached Figure 2As shown in the figure; the fifth step is to perform mutation detection on tissue samples, and the mutation screening filtering conditions are as follows: (a) using the white blood cell test results as a control to remove germline mutations; (b) for hotspot mutations, the mutation abundance ≥ 0.1% is the mutation screening threshold; (c) for non-hotspot mutations, if they are detected in both tissues and plasma, the mutation abundance ≥ 0.1% is used as the mutation screening threshold; (d) for non-hotspot mutations, if they are not detected in tissues, the mutation abundance ≥ 0.5% detected in at least one plasma sample is used as the mutation screening threshold; the sixth step is to divide the mutation detection tissue categories into new categories: preoperative detection (preO), intraoperative detection (pv), only preoperative detection but not intraoperative detection (onlypreO), only intraoperative detection but not preoperative detection (onlypv), and intraoperative and preoperative detection (both), as shown in the figure. Figure 3 and attached Figure 4 As shown; Step 7, combined with imaging analysis, for the enrolled stage II and III patients, although medical imaging did not show the presence of peripheral organ metastases, the mutation detection in tissue samples showed that some patients already had micrometastases, and the mutation abundance of the commonly detected mutations in the patients' preoperative peripheral venous blood and intraoperative portal vein blood samples all met the following conditions: the mutation abundance of the commonly detected mutations in portal vein blood / the mutation abundance of the commonly detected mutations in peripheral venous blood ≤ 2 / 3, as shown in the attached Figure 5 shown.

[0037] Example 2 Clinical Assisted Application Verification In the first step, 84 patients with stage II and III colorectal cancer were enrolled. These patients did not show metastatic lesions in peripheral organs in medical imaging analysis, but mutation detection of tissue samples showed that some patients may have micrometastases. In the second step, 84 patients with colorectal cancer who had no signs of metastasis in imaging but were found to have potential metastatic risk through genetic testing were enrolled. In the third step, sample collection: (a) Before the patient's surgery, peripheral venous blood samples were collected to measure the abundance of gene mutations; (b) During the patient's surgery, portal vein blood samples were collected for mutation abundance detection; (c) During the patient's surgery, tumor tissue samples were collected for mutation detection as a benchmark. In the fourth step, highly sensitive mutation detection technology, such as digital PCR, NGS or other technologies that can accurately quantify mutation abundance, was used to ensure that small differences in mutation abundance could be detected in peripheral venous blood and portal vein blood; (d) Common mutation detection: Through genomic analysis, common mutation sites were found in peripheral venous blood, portal vein blood and tumor tissue, and the abundance of mutations in each sample was calculated. The fifth step is to compare the abundance of common mutation sites in portal vein blood and peripheral venous blood, calculate the mutation abundance ratio, determine whether the mutation abundance ratio is less than or equal to 2 / 3, and associate it with the abundance of mutations in tissue samples. The sixth step is grouping and analysis: patients with micrometastases confirmed by tissue sample mutation detection are divided into the metastasis group; (b) patients with no metastasis in both imaging and histology are divided into the non-metastasis group. Step 7: hypothesis verification. (a) hypothesis: for cancer patients, the mutation abundance in portal vein blood is higher than that in peripheral venous blood, and when the ratio is ≤2 / 3, it indicates that the patient has metastasis; (b) statistical analysis, such as t-test and Mann-Whitney U test, is used to verify the significant difference in mutation abundance ratios between different patient groups; Step 8: clinical verification. Follow-up is performed to observe the clinical metastasis progress of patients 6 or 12 months after surgery, and the abundance ratio in genetic testing is correlated with clinical metastasis to evaluate whether the ratio can be used as a predictive indicator for colorectal cancer metastasis; Step 9: result interpretation. (a) If patients with an abundance ratio ≤ 2 / 3 have a higher detection rate of micrometastases or metastases are found during the follow-up period, it is verified that the ratio can be used as an early predictive marker for colorectal cancer metastasis; (b) On the contrary, if patients with a ratio greater than 2 / 3 have a relatively low risk of metastasis, it means that the ratio is reliable in predicting metastasis; When the mutation abundance ratio (mutation abundance in portal vein blood / mutation abundance in peripheral venous blood) is greater than 2 / 3, patients have a lower risk of metastasis, indicating that this ratio can be used as a reliable predictor of colorectal cancer metastasis. There are several key points to explain this phenomenon. Because the mutation abundance in portal vein blood reflects the mutation load in the colorectal cancer microenvironment, while the mutation abundance in peripheral venous blood reflects the spread of tumor cells outward.If the mutation abundance in portal vein blood is relatively high (ratio greater than 2 / 3), this means that the active mutations of the tumor are more concentrated in the primary lesion, and its tumor cells are still confined to the local or primary site, and have not yet broken through the local barrier (such as the vascular wall, basement membrane, etc.), and there is no significant external metastatic power, indicating a relatively stable state of the disease. Because it has not spread to the peripheral venous blood. This indicates that the tumor has not yet entered a high metastatic state, so the risk of metastasis is low. On the contrary, if the mutation abundance in portal vein blood is relatively low (≤2 / 3), it indicates that the mutation abundance in peripheral venous blood is high, suggesting that tumor cells have begun to spread outward and are more likely to metastasize to distant sites. If patients with a ratio greater than 2 / 3 do show a lower risk of metastasis during follow-up, and this is consistently verified in multiple independent follow-ups, then the mutation abundance ratio can be regarded as a negatively correlated indicator of metastatic risk and has a strong predictive ability. Statistically, using Cox regression or logistic regression analysis methods, it is assumed that a high gene abundance ratio is associated with a low risk, and it is found to be significantly associated through testing, with a p value of less than 0.05, further supporting the ratio as an effective biomarker for predicting metastasis. Clinically, if this ratio can be obtained through intraoperative or postoperative genetic testing, and a lower risk of metastasis can be predicted based on a mutation abundance ratio greater than 2 / 3, this means that doctors can adopt a more conservative treatment strategy for these patients to avoid overtreatment (such as unnecessary chemotherapy or radiotherapy). At the same time, this predictive indicator can also help doctors identify patients with high risk of metastasis earlier and take more active treatment interventions in time. In summary, when a mutation abundance ratio greater than 2 / 3 is significantly associated with a low risk of metastasis, this indicates that the tumor may not have reached the critical point of metastasis, and its metastasis risk is predicted to be low, which can be used as a reliable biomarker and prediction tool for the assessment of metastasis risk of colorectal cancer. Step 10. The experimental results show that the mutation abundance ratio of 2 / 3 proposed in Example 1 can be used as an effective indicator for early screening or prediction of metastasis risk. Through this study, the individualized treatment strategy for patients with colorectal cancer is optimized, especially when no metastasis is detected by imaging. Further testing of the mutation abundance ratio of 2 / 3 in portal vein blood relative to peripheral venous blood can be used as an effective means of predicting micrometastasis of colorectal cancer.

[0038] Example 3 KEGG analysis and verification In the first step, KEGG enrichment analysis was performed on the mutations detected in the high ratio group. In the second step, KEGG enriched pathways were screened using the Bonferroni-corrected P value <= 0.05 as the standard, and pathways not related to colorectal cancer (such as other cancer pathways) were excluded. In the third step, the variable "whether the pathway function is affected" (binary variable, yes, no) was defined. If a mutation was detected in any gene in the pathway, it was considered that the function of the pathway might be affected. In the fourth step, logistic regression was used to compare the difference in "whether the pathway function is affected" between the control group and the recurrence group, and P value <= 0.05 was used as the screening standard for significant differences. The results are shown in the attached figure. Figure 6 As shown in the figure, there is no significant difference between the pathway groups, and the OR is greater than 1. This further indicates that a lower risk of metastasis can be predicted clinically based on a mutation abundance ratio greater than 2 / 3. In other words, doctors can adopt a more conservative treatment strategy for these patients to avoid overtreatment (such as unnecessary chemotherapy or radiotherapy).

[0039] Example 4 According to the process of Example 1-3, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens or ctDNA fragmentation patterns are selected as other markers to measure the residual tumor and recurrence of colorectal cancer patients. Combined with statistical analysis and clinical verification, it was found that the thresholds for copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens or ctDNA fragmentation patterns as other markers for measuring the residual tumor and recurrence of colorectal cancer patients were all values ​​less than 1. In addition, the value of the content of other markers detected in the portal vein blood of the patient during surgery / the value of the content of other markers detected in the peripheral venous blood was less than the threshold value, and a higher detection rate of micrometastases was found or metastasis was found during the follow-up period. At the same time, patients whose values ​​of the content of other markers detected in the portal vein blood during surgery / the content of other markers detected in the peripheral venous blood were greater than the threshold value had a relatively low risk of metastasis. These research results show that the ratio of the content of other markers detected in the portal vein blood during surgery to the content of other markers detected in peripheral venous blood is reliable for measuring tumor residual and recurrence. Among them, the thresholds for measuring tumor residual and recurrence of the copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens, and ctDNA fragmentation patterns of colorectal cancer co-detected mutations are 0.75, 0.84, 0.87, 0.92, 0.85, 0.78, and 0.96, respectively.

[0040] Example 5 According to the process of Example 1-3, the mutation abundance of the commonly detected mutations, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens or ctDNA fragmentation patterns are respectively selected as markers to measure the tumor residual and recurrence of patients with abdominal organ tumors. Combined with statistical analysis and clinical verification, it is found that the thresholds for measuring the tumor residual and recurrence of patients with abdominal organ tumors using the mutation abundance of the commonly detected mutations, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens or ctDNA fragmentation patterns are all values ​​less than 1. In addition, when the ratio of the content of the commonly detected markers in the portal vein or its tributary venous blood during the operation to the content of the same detected markers in the peripheral venous blood is less than the threshold, it is found that there is a higher detection rate of micrometastases or metastasis is found during the follow-up period. At the same time, patients whose values ​​of the content of the commonly detected markers in the portal vein or its tributary venous blood during the operation / the content of the same detected markers in the peripheral venous blood are greater than the threshold have a relatively low risk of metastasis. These research results indicate that the ratio of the content of commonly detected markers in the portal vein or its tributary venous blood during surgery to the content of commonly detected markers in peripheral venous blood is reliable for measuring tumor residual and recurrence. Among them, the thresholds for measuring tumor residual and recurrence of the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens, and ctDNA fragmentation patterns of commonly detected mutations in gastric cancer are 0.69, 0.77, 0.81, 0.89, 0.95, 0.92, and 0.90, respectively; while the thresholds for measuring tumor residual and recurrence of the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens, and ctDNA fragmentation patterns of commonly detected mutations in pancreatic cancer are 0.61, 0.83, 0.70, 0.78, 0.65, 0.87, and 0.74, respectively.

[0041] Example 6 According to the process of Example 1-3, the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens or ctDNA fragmentation patterns of the commonly detected mutations are respectively selected as markers to measure the tumor residual and recurrence of patients with pelvic organ tumors. Combined with statistical analysis and clinical verification, it was found that the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens or ctDNA fragmentation patterns of the commonly detected mutations were other markers for measuring the tumor residual and recurrence of patients with pelvic organ tumors, and all were values ​​less than 1. In addition, when the ratio of the content of the commonly detected marker in the intraoperative ovarian vein or its tributary venous blood / the content of the same detected marker in the peripheral venous blood is less than the threshold, a higher detection rate of micrometastases is found or metastasis is found during the follow-up period. At the same time, patients whose intraoperative ovarian vein or its tributary venous blood has a value greater than the threshold for the content of the commonly detected marker / the content of the same detected marker in the peripheral venous blood have a relatively low risk of metastasis. These research results indicate that the ratio of the content of commonly detected markers in the ovarian vein or its tributary venous blood during surgery to the content of commonly detected markers in peripheral venous blood is reliable for measuring tumor residual and recurrence. Among them, the thresholds for measuring tumor residual and recurrence for the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens, and ctDNA fragmentation patterns of commonly detected mutations in ovarian cancer are 0.50, 0.81, 0.74, 0.68, 0.90, 0.83, and 0.94, respectively.

[0042] Example 7 According to the process of Example 1-3, the mutation abundance of the commonly detected mutations, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens or ctDNA fragmentation patterns are selected as markers to measure the tumor residual and recurrence of patients with pelvic organ tumors. Combined with statistical analysis and clinical verification, it is found that the thresholds for the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens or ctDNA fragmentation patterns of the commonly detected mutations are other markers for measuring the tumor residual and recurrence of patients with pelvic organ tumors are all values ​​less than 1. In addition, when the ratio of the content of the commonly detected marker in the intraoperative uterine vein or its tributary venous blood / the content of the same detected marker in the peripheral venous blood is less than the threshold, it is found that there is a higher detection rate of micrometastases or metastasis is found during the follow-up period. At the same time, patients whose intraoperative uterine vein or its tributary venous blood content / the content of the same detected marker in the peripheral venous blood is greater than the threshold have a relatively low risk of metastasis. These research results indicate that the ratio of the content of commonly detected markers in the uterine vein or its tributary venous blood during surgery to the content of commonly detected markers in peripheral venous blood is reliable for measuring tumor residual and recurrence. Among them, the thresholds for measuring tumor residual and recurrence for the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens, and ctDNA fragmentation patterns of commonly detected mutations in uterine cancer are 0.41, 0.72, 0.90, 0.94, 0.68, 0.55, and 0.79, respectively.

[0043] Example 8 According to the process of Example 1-3, the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens or ctDNA fragmentation patterns of the commonly detected mutations are respectively selected as markers to measure the tumor residual and recurrence of patients with breast, chest wall and other chest structure tumors. Combined with statistical analysis and clinical verification, it is found that the thresholds for the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens or ctDNA fragmentation patterns of the commonly detected mutations are other markers for measuring the tumor residual and recurrence of patients with breast, chest wall and other chest structure tumors are all values ​​less than 1. In addition, when the ratio of the content of the commonly detected marker in the intraoperative breast vein or its tributary venous blood / the content of the same detected marker in the peripheral venous blood is less than the threshold, it is found that it has a higher detection rate of micrometastases or is found to be metastatic during the follow-up period. At the same time, patients whose intraoperative breast vein or its tributary venous blood has a value greater than the threshold for the content of the commonly detected marker / the content of the same detected marker in the peripheral venous blood have a relatively low risk of metastasis. These research results indicate that the ratio of the content of commonly detected markers in the patient's breast vein or its tributary venous blood during surgery to the content of commonly detected markers in peripheral venous blood is reliable for measuring tumor residual and recurrence. Among them, the thresholds for measuring tumor residual and recurrence for the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens, and ctDNA fragmentation patterns of commonly detected breast cancer mutations are 0.56, 0.84, 0.70, 0.96, 0.66, 0.89, and 0.75, respectively.

[0044] Example 9 According to the process of Example 1-3, the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens or ctDNA fragmentation patterns of the commonly detected mutations are respectively selected as markers to measure the tumor residual and recurrence of patients with organ tumors of the urinary system and endocrine system. Combined with statistical analysis and clinical verification, it is found that the thresholds for the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens or ctDNA fragmentation patterns of the commonly detected mutations are other markers for measuring the tumor residual and recurrence of patients with organ tumors of the urinary system and endocrine system are all values ​​less than 1. In addition, when the ratio of the content of the commonly detected marker in the renal vein or its tributary venous blood during the operation / the content of the same detected marker in the peripheral venous blood is less than the threshold value, it is found that there is a higher detection rate of micrometastases or metastasis is found during the follow-up period. At the same time, patients whose values ​​of the content of the commonly detected marker in the renal vein or its tributary venous blood during the operation / the content of the same detected marker in the peripheral venous blood are greater than the threshold value have a relatively low risk of metastasis. These research results indicate that the ratio of the content of commonly detected markers in the renal vein or its tributary venous blood during surgery to the content of commonly detected markers in peripheral venous blood is reliable for measuring tumor residual and recurrence. Among them, the thresholds for measuring tumor residual and recurrence for the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens, and ctDNA fragmentation patterns of commonly detected mutations in renal cancer are 0.82, 0.65, 0.51, 0.92, 0.83, 0.51, and 0.44, respectively.

[0045] Example 10 According to the process of Example 1-3, the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens or ctDNA fragmentation patterns of the co-detected mutations are respectively selected as markers to measure the tumor residual and recurrence of patients with organ tumors of the central nervous system. Combined with statistical analysis and clinical verification, it is found that the thresholds for measuring the tumor residual and recurrence of patients with organ tumors of the central nervous system by the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens or ctDNA fragmentation patterns of the co-detected mutations are all values ​​less than 1. In addition, when the ratio of the content of the co-detected marker in the intraoperative cerebral vein or its tributary venous blood / the content of the same detected marker in the peripheral venous blood is less than the threshold value, a higher detection rate of micro-metastases is found or metastasis is found during the follow-up period. At the same time, patients whose intraoperative cerebral vein or its tributary venous blood co-detected marker content / the content of the same detected marker in the peripheral venous blood is greater than 1 have a relatively low risk of metastasis. These research results indicate that the ratio of the content of commonly detected markers in the blood of the cerebral vein or its tributaries during surgery to the content of commonly detected markers in peripheral venous blood is reliable for measuring tumor residual and recurrence. Among them, the thresholds for measuring tumor residual and recurrence for the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens, and ctDNA fragmentation patterns of commonly detected mutations in brain cancer are 0.39, 0.58, 0.93, 0.86, 0.73, 0.65, and 0.80, respectively.

[0046] Embodiment 11 According to the process of Example 1-3, the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens or ctDNA fragmentation patterns of the co-detected mutations are respectively selected as markers to measure the tumor residual and recurrence of patients with organ tumors of the urinary system. Combined with statistical analysis and clinical verification, it is found that the thresholds for the co-detected mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens or ctDNA fragmentation patterns as other markers for measuring the tumor residual and recurrence of patients with organ tumors of the urinary system are all values ​​less than 1. In addition, when the ratio of the content of the co-detected markers in the intraoperative bladder vein and its tributary venous blood / the content of the same detected markers in the peripheral venous blood is less than the threshold, it is found that there is a higher detection rate of micro-metastases or metastasis is found during the follow-up period. At the same time, patients whose intraoperative bladder vein and its tributary venous blood co-detected markers / the content of the same detected markers in the peripheral venous blood are greater than the threshold have a relatively low risk of metastasis. These research results indicate that the ratio of the content of commonly detected markers in the bladder vein and its tributary venous blood during surgery to the content of commonly detected markers in peripheral venous blood is reliable for measuring tumor residual and recurrence. Among them, the thresholds for measuring tumor residual and recurrence for the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens, and ctDNA fragmentation patterns of commonly detected mutations in bladder cancer are 0.51, 0.62, 0.93, 0.69, 0.79, 0.82, and 0.91, respectively.

[0047] Example 12 According to the process of Example 1-3, the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens or ctDNA fragmentation patterns of the commonly detected mutations are respectively selected as markers to measure the tumor residual and recurrence of patients with organ tumors of the liver and its adjacent organs and systems. Combined with statistical analysis and clinical verification, it was found that the thresholds for the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens or ctDNA fragmentation patterns of the commonly detected mutations as other markers for measuring the tumor residual and recurrence of patients with organ tumors of the liver and its adjacent organs and systems were all values ​​less than 1. In addition, when the ratio of the content of the commonly detected marker in the intraoperative hepatic vein or its tributary venous blood / the content of the same detected marker in the peripheral venous blood is less than the threshold, it is found that there is a higher detection rate of micrometastases or metastasis is found during the follow-up period. At the same time, patients whose intraoperative hepatic vein or its tributary venous blood has a value greater than the threshold for the content of the commonly detected marker / the content of the same detected marker in the peripheral venous blood have a relatively low risk of metastasis. These research results all indicate that the ratio of the content of commonly detected markers in the hepatic vein or its tributary venous blood during surgery to the content of commonly detected markers in peripheral venous blood is reliable for measuring tumor residual and recurrence. Among them, the thresholds for measuring tumor residual and recurrence for the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens, and ctDNA fragmentation patterns of commonly detected mutations in liver cancer are 0.63, 0.83, 0.95, 0.68, 0.74, 0.83, and 0.51, respectively.

[0048] Embodiment 13 According to the process of Example 1-3, the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens or ctDNA fragmentation patterns of the commonly detected mutations are respectively selected as markers to measure the tumor residual and recurrence of patients with organ tumors of the lung and bronchial system. Combined with statistical analysis and clinical verification, it was found that the thresholds for the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens or ctDNA fragmentation patterns of the commonly detected mutations as other markers for measuring the tumor residual and recurrence of patients with organ tumors of the lung and bronchial system were all values ​​less than 1. In addition, when the ratio of the content of the commonly detected marker in the intraoperative pulmonary vein or its tributary venous blood / the content of the same detected marker in the peripheral venous blood is less than the threshold, there is a higher detection rate of micrometastases or metastasis is found during the follow-up period. At the same time, patients whose values ​​of the content of the commonly detected marker in the intraoperative pulmonary vein or its tributary venous blood / the content of the same detected marker in the peripheral venous blood are greater than the threshold have a relatively low risk of metastasis. These research results all indicate that the ratio of the content of commonly detected markers in the pulmonary vein or its tributary venous blood during surgery to the content of commonly detected markers in peripheral venous blood is reliable for measuring tumor residual and recurrence. Among them, the thresholds for measuring tumor residual and recurrence for the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens, and ctDNA fragmentation patterns of commonly detected mutations in lung cancer are 0.74, 0.92, 0.67, 0.63, 0.51, 0.76, and 0.88, respectively.

[0049] Embodiment 14 According to the process of Example 1-3, the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens or ctDNA fragmentation patterns of the commonly detected mutations are respectively selected as markers to measure the tumor residual and recurrence of patients with organ tumors of the esophagus and adjacent organs. Combined with statistical analysis and clinical verification, it was found that the thresholds for measuring the tumor residual and recurrence of patients with organ tumors of the esophagus and adjacent organs by the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens or ctDNA fragmentation patterns of the commonly detected mutations are all values ​​less than 1. In addition, when the ratio of the content of the commonly detected marker in the intraoperative esophageal vein or its tributary venous blood / the content of the same detected marker in the peripheral venous blood is less than the threshold, there is a higher detection rate of micrometastases or metastasis is found during the follow-up period. At the same time, patients whose intraoperative esophageal vein or its tributary venous blood has a value greater than the threshold for the content of the commonly detected marker / the content of the same detected marker in the peripheral venous blood have a relatively low risk of metastasis. These research results indicate that the ratio of the content of commonly detected markers in the esophageal vein or its tributary venous blood during surgery to the content of commonly detected markers in peripheral venous blood is reliable for measuring tumor residual and recurrence. Among them, the thresholds for measuring tumor residual and recurrence for the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens, and ctDNA fragmentation patterns of commonly detected mutations in esophageal cancer are 0.45, 0.63, 0.94, 0.72, 0.61, 0.86, and 0.82, respectively.

[0050] Embodiment 15 According to the process of Example 1-3, the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens or ctDNA fragmentation patterns of the commonly detected mutations are respectively selected as markers to measure the tumor residual and recurrence of patients with organ tumors of the prostate and adjacent organs. Combined with statistical analysis and clinical verification, it is found that the thresholds for measuring the tumor residual and recurrence of patients with organ tumors of the prostate and adjacent organs by the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens or ctDNA fragmentation patterns of the commonly detected mutations are all less than 1. In addition, when the ratio of the content of the commonly detected markers in the intraoperative prostate vein or its tributary venous blood / the content of the same detected markers in the peripheral venous blood is less than the threshold, there is a higher detection rate of micrometastases or metastasis is found during the follow-up period. At the same time, patients whose intraoperative prostate vein or its tributary venous blood has a value greater than the threshold for the content of the commonly detected markers / the content of the same detected markers in the peripheral venous blood have a relatively low risk of metastasis. All these indicate that the ratio of the content of commonly detected markers in the blood of the prostate vein or its tributaries during surgery to the content of commonly detected markers in peripheral venous blood is reliable for measuring tumor residual and recurrence. Among them, the thresholds for measuring tumor residual and recurrence for the mutation abundance, copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens, and ctDNA fragmentation patterns of commonly detected mutations in prostate cancer are 0.52, 0.92, 0.61, 0.76, 0.87, 0.94, and 0.83, respectively.

[0051] The contents explained in the above embodiments should be understood as these embodiments are only used to more clearly illustrate the present invention, and are not used to limit the scope of the present invention. After reading the present invention, various equivalent forms of modifications to the embodiments made by those skilled in the art fall within the scope defined by the claims attached to the present invention.

Claims

1. A method for assisting in measuring tumor residual and recurrence, characterized in that: The method comprises the following steps: a first step, collecting blood samples from the patient's peripheral veins before surgery; a second step, collecting blood samples from the patient's tumor organ drainage veins during surgery; a third step, extracting and analyzing ctDNA from the collected patient's peripheral venous blood and tumor organ drainage venous blood respectively; a fourth step, using molecular biology techniques to quantitatively analyze specific mutations or other markers in ctDNA, comparing the mutation abundance or other marker content of ctDNA in the tumor organ drainage venous blood and the peripheral venous blood, and calculating the ratio of the mutation abundance or other marker content of the commonly detected mutations in the tumor organ drainage venous blood and the peripheral blood; a fifth step, combining imaging analysis to determine whether medical images do not show the presence of peripheral organ metastases but are present in the mutation layer The screen shows the ratio of the mutation abundance or other marker content of the mutations detected in the venous blood draining the tumor organ and the peripheral blood of the patient who already has micrometastases, and uses it as an auxiliary measure of the threshold for tumor residual and recurrence. If the mutation abundance or other marker concentration of the mutations detected in the venous blood draining the tumor organ and the peripheral blood is less than or equal to the threshold, it can assist in diagnosing the presence of tumor micrometastases in the patient's body, that is, the presence of tumor residual or recurrence; the specific mutations or other markers detected in the venous blood draining the tumor organ and the peripheral venous blood are from the same gene, and the other markers include copy number variation, DNA methylation, gene rearrangement, microsatellite instability, epigenetic markers, tumor neoantigens, and ctDNA fragmentation patterns.

2. A method for assisting in measuring tumor residual and recurrence according to claim 1, characterized in that: The molecular biology technology is one or a combined application of digital PCR, qPCR, NGS, BEAMing, ARMS-PCR, ddPCR, CAPP-Seq, SHERLOCK, MassARRAY, LAMP, and Sanger sequencing.

3. A method for assisting in measuring tumor residual and recurrence according to claim 1, characterized in that: The tumors are abdominal organ tumors, pelvic organ tumors, breast, chest wall and other chest structure tumors, urinary system and endocrine system organ tumors, central nervous system organ tumors, urinary system organ tumors, liver and its adjacent organs and systems, lung and bronchial system organ tumors, esophagus and adjacent organs, prostate and adjacent organs.

4. A method for assisting in measuring tumor residual and recurrence according to claim 1, characterized in that: The threshold value for assisting in measuring tumor residual and recurrence is a value less than 1.

5. A method for assisting in measuring tumor residual and recurrence according to claim 1, characterized in that: The tumor is colorectal cancer, the organ drainage venous blood sampling location for colorectal cancer is the portal vein, and the threshold for assisting in measuring residual and recurrence of colorectal cancer is the ratio of the mutation abundance of mutations detected jointly in portal vein blood and peripheral blood, and the threshold is 2 / 3.

6. A method for assisting in measuring tumor residual and recurrence according to claim 1, characterized in that: The tumor is colorectal cancer, the organ drainage vein blood sampling location of the colorectal cancer is the portal vein, and the threshold value for assisting in measuring the residual and recurrence of colorectal cancer is the ratio of the content of other markers detected jointly in the portal vein blood and the peripheral blood, and the threshold value is a value less than 1.

7. A method for assisting in measuring tumor residual and recurrence according to claim 1, characterized in that: The method provides a device for assisting in measuring tumor residual and recurrence, comprising: (1) a data acquisition module, used for quantitatively analyzing specific mutations or other markers in ctDNA, obtaining quantitative data of specific mutations or other markers in ctDNA and performing quality control; (2) a comparison module, used for determining specific mutations or other markers detected in common in ctDNA of tumor organ drainage venous blood and peripheral venous blood; (3) an analysis module, used for determining the mutation abundance of specific mutations detected in common in ctDNA of tumor organ drainage venous blood and peripheral venous blood or the content ratio value of other markers; (4) a reporting module, which gives a conclusion for assisting in measuring tumor residual and recurrence. If the mutation abundance ratio value of specific mutations detected in common in ctDNA of drainage venous blood and peripheral blood or the content ratio value of other markers is ≤ a threshold value, it indicates that micro-metastasis of tumor already exists in the patient, that is, tumor residual or recurrence exists.

8. A method for assisting in measuring tumor residual and recurrence according to claim 1, characterized in that: The method provides a computer-readable storage medium, wherein the computer-readable storage medium includes a program, and the program can be executed by a processor to implement the above-mentioned method for assisting in measuring tumor residual and recurrence.

9. A method for assisting in measuring tumor residual and recurrence according to claim 1, characterized in that: The method provides the device described in claim 7, the use of the storage medium described in claim 8 in preparing the device, and the use of the device to assist in measuring tumor residue and recurrence, assist in guiding targeted drug use, assist in cancer treatment monitoring, and assist in cancer prognosis assessment.

10. The method of assisting in measuring tumor residual and recurrence according to claim 1, characterized in that: The method provides an application of a specific mutation in ctDNA, other markers or a combination thereof in the preparation of tumor prevention and treatment drugs and / or the preparation of tumor detection reagents.