Prognostic evaluation system for fertility-sparing treatment of endometrial cancer

Abstract

The present invention discloses a prognosis evaluation system for endometrial cancer fertility-preserving treatment. The present invention provides a computer device, comprising a memory, a processor, and a computer program stored in the memory; the processor executes the computer program to implement the following steps: receiving cholesterol ester / total fat content data in tumor tissues of several known sensitive / insensitive endometrial cancer patients, and determining a cutoff value for prognosis evaluation of endometrial cancer fertility-preserving treatment based on the data; sensitivity and insensitivity are divided according to whether endometrial cancer patients can achieve complete remission after seven months of fertility-preserving treatment; comparing the cholesterol ester / total fat content data in the tumor tissues of the endometrial cancer patients to be tested with the cutoff value, and determining the prognosis evaluation result of the endometrial cancer patients to be tested after fertility-preserving treatment. The method of the present invention can be used to classify endometrial cancer patients and predict their treatment prognosis of fertility-preserving treatment (progesterone therapy).

Description

Technical Field

[0001] The present invention relates to the field of medical informatics, and in particular to a prognosis evaluation system for endometrial cancer fertility-preserving treatment. Background Art

[0002] The uterus is the most important organ for women to bear children. The occurrence of endometrial cancer will seriously threaten the reproductive function of young women. In recent years, the incidence of endometrial cancer has continued to rise, and there is a clear trend of younger people. The occurrence of endometrial cancer is closely related to diabetes and obesity, and is currently considered a metabolic tumor.

[0003] The conventional treatment for endometrial cancer is total hysterectomy, after which the patient will completely lose fertility, so endometrial cancer fertility-preserving treatment has important social significance. The main treatment for endometrial cancer fertility-preserving treatment is progesterone therapy. According to relevant studies, the complete remission rate of endometrial cancer fertility-preserving treatment is 48.2-77.1%, and the median complete remission time is 6 months. The proportion of patients who do not achieve complete remission after more than 6 months of treatment (clinically defined as progesterone-insensitive patients) is about 45.8%, and the proportion of patients who do not achieve complete remission after more than 12 months (clinically defined as progesterone-resistant patients) is about 33.1%. The longer the treatment time, the more obvious the side effects of the drug will be, and it may also increase the risk of late pregnancy failure.

[0004] Currently, there is no effective method or biomarker to predict the efficacy of fertility-preserving treatment for endometrial cancer patients, and progesterone-insensitive / resistant people cannot be identified in advance before treatment. Therefore, in the clinical practice of fertility-preserving treatment for endometrial cancer, in order to shorten the treatment time, improve the efficacy, and identify progesterone-insensitive / resistant people, efficient and accurate treatment prognosis assessment methods are urgently needed. Summary of the invention

[0005] The purpose of the present invention is to provide a prognosis evaluation system for endometrial cancer fertility-preserving treatment.

[0006] In a first aspect, the present invention claims a computer device.

[0007] The computer device claimed in the present invention comprises a memory, a processor and a computer program stored in the memory; the processor executes the computer program to implement the following steps:

[0008] (A1) Data reception and analysis and processing: Receive data on the content of specific markers in tumor tissues of several known sensitive endometrial cancer patients and several known insensitive endometrial cancer patients, and determine the cutoff value for prognosis evaluation of endometrial cancer fertility-preserving treatment based on the data; the sensitive and insensitive values ​​are divided based on whether the endometrial cancer patients can achieve complete remission after seven months of fertility-preserving treatment, with those who can achieve complete remission being sensitive and those who cannot achieve complete remission being insensitive;

[0009] (A2) Data input: inputting sample data, wherein the sample data is the content data of the specific marker in the tumor tissue of the endometrial cancer patient to be tested;

[0010] (A3) Data comparison and result output: comparing the sample data with the cutoff value, and determining and outputting the prognosis evaluation result of the endometrial cancer patient to be tested after fertility-preserving treatment according to the comparison result;

[0011] The specific marker is cholesterol ester or total fat.

[0012] In a second aspect, the present invention claims a computer program product.

[0013] The computer program product claimed in the present invention comprises a computer program, which implements the steps described in the first aspect above when executed by a processor.

[0014] The computer program product may be a software product that implements its solution mainly through a computer program.

[0015] In a third aspect, the present invention claims a computer-readable storage medium.

[0016] The computer-readable storage medium claimed for protection by the present invention stores a computer program thereon, and when the computer program is executed by a processor, the steps described in the first aspect above are implemented.

[0017] The computer-readable storage medium refers to a carrier for storing data, which may be a tape, disk, floppy disk, CD, magneto-optical disk, ROM, PROM, VCD, DVD, hard disk, flash memory, U disk, CF card, SD card, MMC card, SM card, memory stick (MemoryStick) or xD card, etc.

[0018] In a fourth aspect, the present invention claims protection for a prognostic assessment system (product) for endometrial cancer patients undergoing fertility-sparing treatment.

[0019] The prognostic evaluation system for endometrial cancer patients treated with fertility preservation, which is claimed in the present invention, comprises:

[0020] (B1) Substances (such as reagents and / or instruments) used to detect the content of specific markers in tumor tissues of patients with endometrial cancer;

[0021] (B2) a device; the device comprising unit X and unit Y;

[0022] The unit X is used to determine the cutoff value for prognosis assessment of endometrial cancer fertility preservation treatment, and includes a data receiving module and a data analysis and processing module;

[0023] The data receiving module is configured to receive (B1) the content data of specific markers in tumor tissues of several known sensitive endometrial cancer patients and several known insensitive endometrial cancer patients; the sensitive and insensitive are divided based on whether the endometrial cancer patients can achieve complete remission after seven months of fertility preservation treatment, and the patients who can achieve complete remission are sensitive, and those who cannot achieve complete remission are insensitive;

[0024] The data analysis and processing module is configured to receive the content data of the specific marker in the tumor tissues of the several known sensitive endometrial cancer patients and the several known insensitive endometrial cancer patients sent by the data receiving module, and determine the cutoff value for the prognosis assessment of endometrial cancer fertility-sparing treatment based on the content data of the specific marker in the tumor tissues of the several known sensitive endometrial cancer patients and the several known insensitive endometrial cancer patients;

[0025] The unit Y is used to determine the prognosis evaluation result of the endometrial cancer patient to be tested after fertility preservation treatment, and includes a data input module, a data comparison module and a conclusion output module;

[0026] The data input module is configured to input (B1) the content data of the specific marker in the tumor tissue of the endometrial cancer patient to be tested;

[0027] The data comparison module is configured to receive the content data of the specific marker in the tumor tissue of the endometrial cancer patient to be tested sent by the data input module, retrieve the cutoff value determined in the data analysis and processing module in the unit X, and compare the content data of the specific marker in the tumor tissue of the endometrial cancer patient to be tested with the cutoff value;

[0028] The conclusion output module is configured to receive the comparison result from the data comparison module, and determine and output the prognosis evaluation result of the endometrial cancer patient to be tested after fertility-preserving treatment according to the comparison result;

[0029] The specific marker is cholesterol ester or total fat.

[0030] In the above related aspects, the cutoff value may be any of the following:

[0031] (C1) When the specific marker is cholesterol ester, the content data of the specific marker is the content data of cholesterol ester in tumor tissue, and the cutoff value is 40 μmol / g;

[0032] (C2) When the specific marker is total fat, the content data of the specific marker is the percentage data of fat content in tumor tissue, and the cutoff value is 1.5%.

[0033] Furthermore, determining and outputting the prognosis evaluation result of the endometrial cancer patient to be tested after fertility-sparing treatment according to the comparison result may be performed in any of the following ways:

[0034] (D1) If the cholesterol ester content data in the tumor tissue of the endometrial cancer patient to be tested is greater than or equal to 40 μmol / g, the prognosis of the endometrial cancer patient to be tested after fertility-preserving treatment is poor or a candidate for poor prognosis; if the cholesterol ester content data in the tumor tissue of the endometrial cancer patient to be tested is less than 40 μmol / g, the prognosis of the endometrial cancer patient to be tested after fertility-preserving treatment is good or a candidate for good prognosis;

[0035] (D2) If the fat content percentage data in the tumor tissue of the endometrial cancer patient to be tested is greater than or equal to 1.5%, then the prognosis of the endometrial cancer patient to be tested after fertility-preserving treatment is poor or a candidate for poor prognosis; if the fat content percentage data in the tumor tissue of the endometrial cancer patient to be tested is less than 1.5%, then the prognosis of the endometrial cancer patient to be tested after fertility-preserving treatment is good or a candidate for good prognosis.

[0036] In a fifth aspect, the present invention claims a method for evaluating the prognosis of endometrial cancer patients undergoing fertility-sparing treatment.

[0037] The method for prognosis assessment of endometrial cancer patients treated with fertility preservation as claimed in the present invention may include:

[0038] (E1) Data input: inputting sample data, wherein the sample data is the cholesterol ester content data in the tumor tissue of the endometrial cancer patient to be tested or the fat content percentage data in the tumor tissue;

[0039] (E2) Data comparison and result output: The sample data is compared with the corresponding cutoff value, the cutoff value of the corresponding data on the cholesterol ester content in the tumor tissue is 40 μmol / g, and the cutoff value of the corresponding data on the percentage of fat content in the tumor tissue is 1.5%. Based on the comparison results, the prognosis evaluation result of the endometrial cancer patient to be tested after fertility-preserving treatment is determined in any of the following ways:

[0040] If the cholesterol ester content data in the tumor tissue of the endometrial cancer patient to be tested is greater than or equal to 40 μmol / g, the prognosis of the endometrial cancer patient to be tested after fertility-preserving treatment is poor or a candidate for poor prognosis; if the cholesterol ester content data in the tumor tissue of the endometrial cancer patient to be tested is less than 40 μmol / g, the prognosis of the endometrial cancer patient to be tested after fertility-preserving treatment is good or a candidate for good prognosis;

[0041] If the fat content percentage data in the tumor tissue of the endometrial cancer patient to be tested is greater than or equal to 1.5%, then the prognosis of the endometrial cancer patient to be tested after fertility-preserving treatment is poor or a candidate for poor prognosis; if the fat content percentage data in the tumor tissue of the endometrial cancer patient to be tested is less than 1.5%, then the prognosis of the endometrial cancer patient to be tested after fertility-preserving treatment is good or a candidate for good prognosis.

[0042] In a sixth aspect, the present invention claims protection for the use of a substance for detecting the content of a specific marker in the tumor tissue of an endometrial cancer patient in the preparation of a product for evaluating the prognosis of an endometrial cancer patient undergoing fertility-sparing treatment; the specific marker is total fat or cholesterol ester.

[0043] In the above-mentioned related aspects, the percentage of fat content in the tumor tissue is measured by Oil Red O staining. The percentage of fat content in the tumor tissue is equal to the area of ​​fat droplets divided by the total area of ​​the tumor region.

[0044] In the above-mentioned related aspects, determining the cutoff value for the prognosis evaluation of endometrial cancer fertility-sparing treatment based on the content data of the specific marker in the tumor tissues of the several known sensitive endometrial cancer patients and the several known insensitive endometrial cancer patients is achieved as follows: assuming that the content data of the specific marker in the tumor tissue used to distinguish between sensitive and insensitive endometrial cancer patients is M, then based on M, a sensitivity and / or insensitivity prediction is performed for each individual in the group consisting of the several known sensitive endometrial cancer patients and the several known insensitive endometrial cancer patients, and the M value with the highest degree of consistency between the prediction result (including both specificity and sensitivity) and the actual situation is the cutoff value.

[0045] In the above-mentioned related aspects, the poor prognosis refers to that endometrial cancer patients cannot achieve complete remission after seven months of fertility-preserving treatment; the good prognosis refers to that endometrial cancer patients achieve complete remission within seven months of fertility-preserving treatment.

[0046] In the above-mentioned related aspects, the fertility-preserving treatment is progestin treatment. Further, the progestin is medroxyprogesterone.

[0047] In the above-mentioned related aspects, the substance used to detect the content of a specific marker in the tumor tissue of a patient with endometrial cancer may be any of the following:

[0048] (F1) a reagent that can specifically bind to the specific marker and indicate its content (such as a specific dye or antibody, etc.);

[0049] (F2) It is composed of an instrument capable of detecting the specific marker and a standard substance of the specific marker (such as a high performance liquid chromatograph / enzyme reader and a standard substance, etc.).

[0050] In one embodiment of the present invention, the substance used to detect the cholesterol ester content in tumor tissue includes (or is) a commercial kit for detecting the cholesterol ester content (Elerite #E-BC-F032), which contains a cholesterol standard.

[0051] In another embodiment of the present invention, the substance used to detect the percentage of fat content in tumor tissue includes (or is) Oil Red O dye.

[0052] In the present invention, the endometrial cancer patient is a stage IA endometrial cancer patient.

[0053] Experimental proof: This application proves that the increased total fat content and cholesterol ester content in the tumor tissue of endometrial cancer patients are sensitive markers for poor prognosis of endometrial cancer fertility-sparing treatment (progesterone therapy). The method of the present invention can be used to classify endometrial cancer patients and predict their prognosis of fertility-sparing treatment (progesterone therapy). BRIEF DESCRIPTION OF THE DRAWINGS

[0054] Figure 1 A computer flow chart for the prognosis assessment of fertility-sparing treatment for endometrial cancer according to the present invention.

[0055] Figure 2 Oil red O staining of tumor tissue and analysis of fat content in tumor tissue in patients with endometrial cancer.

[0056] Figure 3 A retrospective clinical trial (training set) to predict the efficacy of fertility-sparing treatment (progestin therapy) for endometrial cancer.

[0057] Figure 4 This is the correlation analysis between various clinical indicators and the efficacy of fertility-preserving treatment (progestin therapy) (training set).

[0058] Figure 5 A retrospective clinical trial (validation set) to predict the efficacy of fertility-sparing treatment (progestin therapy) for endometrial cancer.

[0059] Figure 6This is a correlation analysis between various clinical indicators and the efficacy of fertility-preserving treatment (progestin therapy) (validation set). DETAILED DESCRIPTION

[0060] The present invention is further described in detail below in conjunction with specific embodiments, and the examples provided are only for illustrating the present invention, rather than for limiting the scope of the present invention. The examples provided below can be used as a guide for further improvements by those of ordinary skill in the art, and do not constitute a limitation of the present invention in any way.

[0061] The experimental methods in the following examples, unless otherwise specified, are all conventional methods, and are performed according to the techniques or conditions described in the literature in the field or according to the product instructions. The materials, reagents, etc. used in the following examples, unless otherwise specified, can all be obtained from commercial channels.

[0062] Figure 1 A computer flow chart for the prognosis assessment of fertility-sparing treatment for endometrial cancer according to the present invention.

[0063] In step S1, the content data of specific markers in tumor tissues of several known sensitive endometrial cancer patients and several known insensitive endometrial cancer patients are received, and a cutoff value for prognosis evaluation of endometrial cancer fertility-sparing treatment is determined based on the content data of specific markers in tumor tissues of several known sensitive endometrial cancer patients and several known insensitive endometrial cancer patients, wherein the sensitive and insensitive values ​​are divided based on whether the endometrial cancer patients can achieve complete remission after seven months of fertility-sparing treatment, and the sensitive values ​​are those who can achieve complete remission, and the insensitive values ​​are those who cannot achieve complete remission;

[0064] In step S2, sample data is input, wherein the sample data is the content data of a specific marker (cholesterol ester or total fat) in the tumor tissue of the endometrial cancer patient to be tested;

[0065] In step S3, the sample data in S2 is compared with the cutoff value in S1;

[0066] In step S4, based on the comparison result of S3, the prognosis evaluation result of the endometrial cancer patient to be tested after fertility-sparing treatment is determined and output.

[0067] The method used in the following examples to detect the percentage (%) of fat content in tumor tissue of endometrial cancer patients is Oil Red O staining.

[0068] The specific steps of Oil Red O staining are as follows: The tumor tissue specimens of endometrial cancer to be tested are directly embedded in OCT (optimal cutting temperature compound, Sakura #4583) to prepare frozen sections with a thickness of 10 μm. The frozen sections are stained using the Oil Red O staining kit (Solabo #G1261) according to the following steps: (1) Wash twice with distilled water for 3 minutes each time; (2) Wash the sections in 60% isopropanol for 30 seconds; (3) Wash the sections in modified Oil Red O staining solution (covered) and seal for 15 minutes; (4) Wash the sections in 60% isopropanol for 5 seconds to remove the staining solution and wash with running water for 1 minute; (5) Counterstain the nucleus with Mayer's hematoxylin staining solution for 2 minutes; (6) Rinse with tap water for 10 minutes to reverse blue; (7) Wash once with distilled water and dry the surrounding water with filter paper; (8) Seal the sections with glycerol gelatin.

[0069] The staining effect of Oil Red O is shown in Figure 2 The steps for staining image data analysis are as follows: (1) Scan the stained slides with a slice scanner (Shengqiang SQS-40P) at a scanning magnification of 40×. Select three tumor sites for each slice and capture the field of view. The field of view area is 7019 pixels × 3410 pixels; (2) Open the image with ImageJ software and use the RBG color separation function to obtain the blue channel field of view image; (3) Use the threshold function to process the image and set the threshold to 0-90; (4) Use the Measure function to measure the image and obtain the area of ​​lipid droplets; (5) Divide the area of ​​lipid droplets by the total area of ​​the tumor region to obtain the percentage of fat content in the tumor tissue. The average percentage of fat content in the three fields of view is output as the detection value.

[0070] The method used in the following examples for detecting the content of cholesterol ester (μmol / g) in tumor tissue of patients with endometrial cancer is as follows: (1) prepare a standard substance (5.17 mmol / L cholesterol standard substance) according to the instructions of the cholesterol ester content detection kit (Elerite #E-BC-F032); (2) weigh and homogenize the tumor tissue of the patient with endometrial cancer to be tested, and dilute the homogenate to 300 μL; (3) set a standard well, a test well and a blank control well in a 96-well ELISA plate, and the sample volume of each well is 50 μL; (4) add 50 μL of color developer 1 to each well, shake the plate for 10 seconds, and incubate at 37°C in the dark for 10 min. The fluorescence value of each well at an excitation wavelength of 535 nm and an emission wavelength of 590 nm was detected on an ELISA reader (Synergy LX) to obtain the total cholesterol content in the sample; (5) The standard wells, test wells and blank control wells were reset, and the sample volume of each well was 50 μL; (6) 50 μL of color developer 2 was added to each well, the plate was shaken for 10 seconds, and incubated at 37°C in the dark for 10 minutes. The fluorescence value of each well at an excitation wavelength of 535 nm and an emission wavelength of 590 nm was detected on an ELISA reader (Synergy LX) to obtain the free cholesterol content in the sample; (7) The cholesterol ester content was obtained by subtracting the free cholesterol content from the total cholesterol content, and this content was divided by the tissue weight to obtain the cholesterol ester content per gram of tumor tissue.

[0071] The inclusion criteria for endometrial cancer cases in the following examples are: (1) patients under 45 years old with a strong desire to preserve fertility; (2) the histopathological type is endometrial adenocarcinoma, well-differentiated (G1 / G2); (3) imaging examinations confirm that the tumor is confined to the endometrium, without extrauterine invasion and lymph node metastasis; (4) histopathological detection of progesterone receptor positivity; (5) fully informed consent and good follow-up conditions.

[0072] The criteria for grouping endometrial cancer cases in the following examples are as follows: (1) those with fertility disorders and contraindications; (2) those whose pre-treatment evaluation indicates cervical infiltration, extrauterine invasion, or lymph node metastasis; (3) those with contraindications to progestin therapy; (4) those with a family history of hereditary tumors such as Lynch syndrome; (5) those with combined malignant tumors in other parts of the body; and (6) those with poor compliance, inability to cooperate with clinical treatment, and inability to bear the risks associated with treatment.

[0073] Example 1: Establishment of a prognosis prediction cohort for endometrial cancer fertility-sparing treatment (progestin therapy)

[0074] like Figure 3The present invention established a retrospective clinical trial to identify factors related to the prognosis of fertility-preserving therapy (progestin therapy) for endometrial cancer. A total of 40 patients with endometrial cancer in stage IA who were interested in fertility-preserving therapy were enrolled. Except for one patient who gave up fertility-preserving therapy, the remaining 39 patients collected peripheral blood and tumor biopsy samples before treatment and performed relevant tests. The test indicators and results are shown in Table 1. Subsequently, these patients were treated with fertility-preserving therapy (progestin therapy, specifically medroxyprogesterone, 500 mg / day, taken orally once a day) according to the standard regimen (refer to the NCCN Endometrial Cancer Clinical Diagnosis and Treatment Guidelines), and follow-up and efficacy evaluation were performed in the third and seventh months of the treatment process, and the patients were divided into a sensitive group (13 patients) and an insensitive group (26 patients) based on whether complete remission could be achieved after seven months of treatment.

[0075]

[0076]

[0077] The occurrence of endometrial cancer is closely related to diabetes and obesity. Therefore, the present invention detects relevant indicators of the enrolled patients, including: the proportion of fat content in tumor tissue, the cholesterol ester content in tumor tissue, lipid accumulation index, visceral fat index, body mass index, high-density lipoprotein, low-density lipoprotein, and free fatty acids.

[0078] The above parameters were analyzed for correlation with the clinical outcomes of the patients' fertility preservation treatment (progestin therapy). Figure 4 As shown. It can be seen that in this clinical trial cohort (training set cohort), the area under the ROC curve of the correlation curve between the proportion of fat content in tumor tissue and prognosis is 0.824 (p=0.0011), and the two are significantly correlated; the area under the ROC curve of the correlation curve between the cholesterol ester content in tumor tissue and prognosis is 0.959 (p<0.0001), and the two are significantly correlated; the area under the ROC curve of the correlation curve between high-density lipoprotein and prognosis is 0.783 (p=0.0044), and the two are significantly correlated. However, parameters such as lipid accumulation index, visceral fat index, body mass index, blood sugar, low-density lipoprotein and free fatty acids are not significantly correlated with treatment and after. Detailed data are shown in Table 2.

[0079]

[0080] According to the ROC curve of the indicator "percentage of fat content in tumor tissue", the optimal cutoff value was determined to be 1.5%. Under this condition, combined with the clinical outcomes, the analysis was performed to obtain Table 3.

[0081]

[0082] That is, if the fat content in the tumor tissue of the endometrial cancer patient to be tested accounts for less than 1.5%, the endometrial cancer patient to be tested is regarded as an endometrial cancer patient who is sensitive to progesterone; if the fat content in the tumor tissue of the endometrial cancer patient to be tested accounts for greater than or equal to 1.5%, the endometrial cancer patient to be tested is regarded as an endometrial cancer patient who is insensitive to progesterone.

[0083] The sensitivity and specificity of the method for predicting poor prognosis using "tumor tissue fat content ratio" are:

[0084] Sensitivity = true positive / (true positive + false negative) = 18 / (18+8) = 69.2%;

[0085] Specificity = true negative / (true negative + false positive) = 11 / (11+2) = 84.6%.

[0086] According to the ROC curve of the indicator "tumor tissue cholesterol ester content", the optimal cutoff value was determined to be 40 μmol / g. Under this condition, combined with the clinical outcomes, the analysis was performed to obtain Table 4.

[0087]

[0088] That is, if the cholesterol ester content in the tumor tissue of the endometrial cancer patient to be tested is less than 40 μmol / g, the endometrial cancer patient to be tested is regarded as an endometrial cancer patient sensitive to progesterone; if the cholesterol ester content in the tumor tissue of the endometrial cancer patient to be tested is greater than or equal to 40 μmol / g, the endometrial cancer patient to be tested is regarded as an endometrial cancer patient insensitive to progesterone.

[0089] The sensitivity and specificity of the method for predicting poor prognosis using "tumor tissue cholesterol ester content" are:

[0090] Sensitivity = true positive / (true positive + false negative) = 22 / (22+4) = 84.6%;

[0091] Specificity = true negative / (true negative + false positive) = 13 / (13 + 0) = 100%.

[0092] According to the ROC curve of the indicator "high-density lipoprotein content", the optimal cutoff value was determined to be 1.1 mmol / L. Under this condition, combined with the clinical outcomes, the analysis was performed to obtain Table 5.

[0093]

[0094] That is, if the high-density lipoprotein content in the peripheral blood of the endometrial cancer patient to be tested is greater than 1.1 mmol / L, the endometrial cancer patient to be tested is regarded as an endometrial cancer patient who is sensitive to progesterone; if the high-density lipoprotein content in the peripheral blood of the endometrial cancer patient to be tested is less than or equal to 1.1 mmol / L, the endometrial cancer patient to be tested is regarded as an endometrial cancer patient who is insensitive to progesterone.

[0095] The sensitivity and specificity of the method for predicting poor prognosis using "high-density lipoprotein content" are:

[0096] Sensitivity = true positive / (true positive + false negative) = 19 / (19+7) = 73.1%;

[0097] Specificity = true negative / (true negative + false positive) = 10 / (10+3) = 76.9%.

[0098] Based on the data obtained from the above clinical trials, the present invention selected three parameters, namely the percentage of fat content in tumor tissue, the cholesterol ester content in tumor tissue and the high-density lipoprotein content in peripheral blood, as sensitive markers for poor prognosis of endometrial cancer with fertility-preserving treatment (progestin therapy), for further testing in subsequent verification cohorts.

[0099] Example 2: Validation cohort of sensitive markers for poor prognosis in endometrial cancer patients undergoing fertility-sparing therapy (progestin therapy)

[0100] like Figure 5 The present invention established a retrospective clinical trial to identify the three biomarkers selected in Example 1 and the factors related to the treatment prognosis of endometrial cancer fertility preservation therapy (progestin therapy). A total of 30 patients with endometrial cancer in stage IA who intended to undergo fertility preservation therapy were enrolled (an independent sample set completely different from the training set in Example 1). Except for one person who gave up fertility preservation therapy, the remaining 29 patients collected peripheral blood and tumor biopsy samples before treatment and performed relevant tests. The test indicators and results are shown in Table 6. Subsequently, these patients were treated with fertility preservation therapy (progestin therapy, specifically medroxyprogesterone, 500 mg / day, orally once a day) according to the standard regimen (refer to the NCCN Endometrial Cancer Clinical Diagnosis and Treatment Guidelines), and follow-up and efficacy evaluation were performed in the third and seventh months of the treatment process, and the patients were divided into sensitive and insensitive groups based on whether complete remission could be achieved after seven months of treatment.

[0101]

[0102] It can be seen that in this clinical trial cohort (validation set cohort), the area under the ROC curve of the correlation curve between fat content in tumor tissue and prognosis is 0.745 (p=0.0253), and the two are significantly correlated; the area under the ROC curve of the correlation curve between cholesterol ester content in tumor tissue and prognosis is 0.899 (p=0.0003), and the two are significantly correlated; the area under the ROC curve of the correlation curve between high-density lipoprotein and prognosis is 0.608 (p=0.324), and there is no correlation between the two. Results and detailed data are shown in Figure 6 and Table 7.

[0103]

[0104] Next, we verified the sensitivity and specificity of the cutoff value of 15% of the "tumor tissue fat content ratio" indicator obtained in Example 1 in the validation cohort. The validation set data is shown in Table 8.

[0105]

[0106] Sensitivity = true positive / (true positive + false negative) = 10 / (10+6) = 62.5%;

[0107] Specificity = true negative / (true negative + false positive) = 9 / (9+4) = 69.2%.

[0108] Next, we obtained the sensitivity and specificity of the cutoff value of 40 μmol / g of the indicator "tumor tissue cholesterol ester content" in Example 1 in the validation cohort. The validation set data is shown in Table 9.

[0109]

[0110] Sensitivity = true positive / (true positive + false negative) = 15 / (15+1) = 93.8%;

[0111] Specificity = true negative / (true negative + false positive) = 11 / (11+2) = 84.6%.

[0112] According to the data obtained from the above clinical trials, the present invention finally confirmed that the two parameters of "tumor tissue fat content ratio" and "tumor tissue cholesterol ester content" can be used as sensitive markers for poor prognosis of endometrial cancer fertility preservation treatment (progesterone therapy). Among them, the "tumor tissue cholesterol ester content" indicator has high sensitivity and specificity for predicting poor prognosis, and is an efficient and accurate prediction indicator; "tumor tissue fat content ratio" is correlated with prognosis, but the sensitivity and specificity of using this indicator to predict poor prognosis are relatively low.

[0113] Example 3: Clinical application of prognostic assessment of fertility-sparing treatment (progestin therapy) for endometrial cancer

[0114] This example uses clinical trials to further test the prognostic evaluation model established and verified in Examples 1 and 2. A total of 32 patients with endometrial cancer in stage IA who intend to undergo fertility preservation treatment were enrolled. All 32 patients underwent biopsy according to the methods in Examples 1 and 2 to detect the total fat content and cholesterol ester content in the tumor tissue, and the patients were divided into a progesterone-sensitive group (13 people, the cholesterol ester content in the tumor tissue was less than 40 μmol / g and the fat content in the tumor tissue accounted for less than 1.5%) and a progesterone-insensitive group (19 people, the cholesterol ester content in the tumor tissue was greater than or equal to 40 μmol / g and the fat content in the tumor tissue accounted for greater than or equal to 1.5%). Among them, 13 people in the sensitive group were treated with fertility preservation treatment (progesterone treatment, specifically medroxyprogesterone, 500 mg / day, orally once a day) according to the standard regimen (refer to the NCCN Endometrial Cancer Clinical Diagnosis and Treatment Guidelines). The insensitive group also received fertility-preserving treatment (progestin therapy, specifically medroxyprogesterone, 500 mg / day, orally once a day) according to the standard regimen (refer to the NCCN Endometrial Cancer Clinical Diagnosis and Treatment Guidelines). The patients were followed up and the efficacy was evaluated at the third and seventh months of treatment.

[0115] The results show:

[0116] Among the 13 patients in the progesterone-sensitive group, except for 3 patients whose treatment was less than three months and whose efficacy could not be evaluated temporarily, 9 of the remaining 10 patients achieved complete remission in seven months, and 1 patient achieved partial remission in the seventh month.

[0117] Among the 19 patients in the progesterone-insensitive group, except for 4 patients who had been treated for less than three months and could not be evaluated for efficacy, the other 15 patients who completed the efficacy evaluation did not achieve complete remission after 3 months of treatment. Among them, 3 patients achieved complete remission after 7 months of treatment, and the remaining 12 patients still did not achieve complete remission after 7 months of treatment.

[0118] The above results further confirm that the prognostic evaluation method for fertility-preserving treatment (progestin therapy) of endometrial cancer established by the present invention can accurately predict the efficacy of progestin-preserving treatment.

[0119] The present invention has been described in detail above. For those skilled in the art, without departing from the purpose and scope of the present invention, and without the need to carry out unnecessary experimental conditions, the present invention can be implemented in a wide range under equivalent parameters, concentrations and conditions. Although the present invention provides specific embodiments, it should be understood that the present invention can be further improved. In a word, according to the principles of the present invention, the application is intended to include any changes, uses or improvements to the present invention, including departure from the disclosed scope in the application, and changes made with conventional techniques known in the art.

Claims

1. A computer device comprising a memory, a processor and a computer program stored in the memory, characterized in that: The processor executes the computer program to implement the following steps: (A1) Data reception and analysis and processing: Receive data on the content of specific markers in tumor tissues of several known sensitive endometrial cancer patients and several known insensitive endometrial cancer patients, and determine the cutoff value for prognosis evaluation of endometrial cancer fertility-preserving treatment based on the data; the sensitive and insensitive values ​​are divided based on whether the endometrial cancer patients can achieve complete remission after seven months of fertility-preserving treatment, with those who can achieve complete remission being sensitive and those who cannot achieve complete remission being insensitive; (A2) Data input: inputting sample data, wherein the sample data is the content data of the specific marker in the tumor tissue of the endometrial cancer patient to be tested; (A3) Data comparison and result output: comparing the sample data with the cutoff value, and determining and outputting the prognosis evaluation result of the endometrial cancer patient to be tested after fertility-preserving treatment according to the comparison result; The specific marker is cholesterol ester or total fat.

2. A computer program product, comprising a computer program, characterized in that: The computer program implements the steps recited in claim 1 when executed by a processor.

3. A computer-readable storage medium having a computer program stored thereon, characterized in that: The computer program implements the steps recited in claim 1 when executed by a processor.

4. A prognostic assessment system for endometrial cancer patients undergoing fertility-sparing treatment, comprising: (B1) a substance for detecting the content of a specific marker in tumor tissue of a patient with endometrial cancer; (B2) Device; The device comprises a unit X and a unit Y; The unit X is used to determine the cutoff value for prognosis assessment of fertility-preserving treatment of endometrial cancer, and includes a data receiving module and a data analysis and processing module; The data receiving module is configured to receive (B1) the content data of specific markers in tumor tissues of several known sensitive endometrial cancer patients and several known insensitive endometrial cancer patients; the sensitive and insensitive are divided based on whether the endometrial cancer patients can achieve complete remission after seven months of fertility preservation treatment, and the patients who can achieve complete remission are sensitive, and those who cannot achieve complete remission are insensitive; The data analysis and processing module is configured to receive the content data of the specific marker in the tumor tissues of the several known sensitive endometrial cancer patients and the several known insensitive endometrial cancer patients sent by the data receiving module, and determine the cutoff value for the prognosis assessment of endometrial cancer fertility-sparing treatment based on the content data of the specific marker in the tumor tissues of the several known sensitive endometrial cancer patients and the several known insensitive endometrial cancer patients; The unit Y is used to determine the prognosis evaluation result of the endometrial cancer patient to be tested after fertility preservation treatment, and includes a data input module, a data comparison module and a conclusion output module; The data input module is configured to input (B1) the content data of the specific marker in the tumor tissue of the endometrial cancer patient to be tested; The data comparison module is configured to receive the content data of the specific marker in the tumor tissue of the endometrial cancer patient to be tested sent by the data input module, retrieve the cutoff value determined in the data analysis and processing module in the unit X, and compare the content data of the specific marker in the tumor tissue of the endometrial cancer patient to be tested with the cutoff value; The conclusion output module is configured to receive the comparison result from the data comparison module, and determine and output the prognosis evaluation result of the endometrial cancer patient to be tested after fertility-preserving treatment according to the comparison result; The specific marker is cholesterol ester or total fat.

5. The system according to claim 4, characterized in that: The cutoff value is any of the following: (C1) When the specific marker is cholesterol ester, the content data of the specific marker is the content data of cholesterol ester in tumor tissue, and the cutoff value is 40 μmol / g; (C2) When the specific marker is total fat, the content data of the specific marker is the percentage data of fat content in tumor tissue, and the cutoff value is 1.5%.

6. The system according to claim 5, characterized in that: Determining and outputting the prognosis evaluation result of the endometrial cancer patient to be tested after fertility-preserving treatment according to the comparison result is performed in any of the following ways: (D1) If the cholesterol ester content data in the tumor tissue of the endometrial cancer patient to be tested is greater than or equal to 40 μmol / g, the endometrial cancer patient to be tested has a poor prognosis or is a candidate for a poor prognosis after fertility-sparing treatment; If the cholesterol ester content data in the tumor tissue of the endometrial cancer patient to be tested is less than 40 μmol / g, the endometrial cancer patient to be tested has a good prognosis or a good candidate prognosis after fertility-preserving treatment; (D2) If the fat content percentage data in the tumor tissue of the endometrial cancer patient to be tested is greater than or equal to 1.5%, then the endometrial cancer patient to be tested has a poor prognosis or is a candidate for a poor prognosis after fertility-preserving treatment; If the fat content ratio in the tumor tissue of the endometrial cancer patient to be tested is less than 1.5%, the endometrial cancer patient to be tested has a good prognosis or is a candidate for a good prognosis after fertility-preserving treatment.

7. A method for evaluating the prognosis of endometrial cancer patients undergoing fertility-sparing treatment, comprising: (E1) Data input: inputting sample data, wherein the sample data is the cholesterol ester content data in the tumor tissue of the endometrial cancer patient to be tested or the fat content percentage data in the tumor tissue; (E2) Data comparison and result output: The sample data is compared with the corresponding cutoff value, the cutoff value of the corresponding data on the cholesterol ester content in the tumor tissue is 40 μmol / g, and the cutoff value of the corresponding data on the percentage of fat content in the tumor tissue is 1.5%. Based on the comparison results, the prognosis evaluation result of the endometrial cancer patient to be tested after fertility-preserving treatment is determined in any of the following ways: If the cholesterol ester content data in the tumor tissue of the endometrial cancer patient to be tested is greater than or equal to 40 μmol / g, the endometrial cancer patient to be tested has a poor prognosis or a candidate poor prognosis after fertility-preserving treatment; If the cholesterol ester content data in the tumor tissue of the endometrial cancer patient to be tested is less than 40 μmol / g, the endometrial cancer patient to be tested has a good prognosis or a good candidate prognosis after fertility-preserving treatment; If the fat content ratio in the tumor tissue of the endometrial cancer patient to be tested is greater than or equal to 1.5%, then the endometrial cancer patient to be tested has a poor prognosis or is a candidate for a poor prognosis after fertility-preserving treatment; If the fat content ratio in the tumor tissue of the endometrial cancer patient to be tested is less than 1.5%, the endometrial cancer patient to be tested has a good prognosis or is a candidate for a good prognosis after fertility-preserving treatment.

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