Methods and materials for evaluating and treating cancer
By detecting specific genetic and protein biomarkers in blood samples, combined with multiple sequencing and aneuploidy detection, the problem of insufficient sensitivity and specificity detection of early cancers in the prior art is solved, and earlier diagnosis and treatment are achieved Chance.
Patent Information
- Application Number
- CN201880066039.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Priority Date
- 2018-02-13
- Filing Date
- 2018-08-07
- Publication Date
- 2025-02-21
- Estimated Expiration
- 2038-10-27
AI Technical Summary
The prior art has problems with insufficient sensitivity and specificity in the detection and treatment of early cancers, especially in pancreatic cancer, ovarian cancer, endometrial cancer and bladder cancer.
The presence of cancer was identified by detecting specific genetic and protein biomarkers in the subject's blood samples, including KRAS, TP53, CA19-9, CEA, HGF, and OPN.
Improves detection sensitivity and specificity for early stage cancer, enabling the identification of cancer before subjects show obvious symptoms, providing an earlier opportunity for diagnosis and treatment.
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Abstract
Claims
1. A kit comprising a) a set of 61 primer pairs, wherein each primer pair comprises a first primer and a second primer, wherein the first primer and the second primer each comprise a portion complementary to a gene or a gene portion selected from the group consisting of NRAS, CTNNB1, PIK3CA, FBXW7, APC, EGFR, BRAF, CDKN2A, PTEN, FGFR2, HRAS, KRAS, AKT1, TP53, PPP2R1A and GNAS, The set of 61 primer pairs amplifies each of the following codons: codons 3-15 of NRAS, codons 54-63 of NRAS, codons 31-39 of CTNNB1, codons 38-47 of CTNNB1, codons 80-90 of PIK3CA, codons 343-348 of PIK3CA, codons 541-551 of PIK3CA, codons 1038-1050 of PIK3CA, codons 361-371 of FBXW7, codons 464-473 of FBXW7, codons 473-483 of FBXW7, codons 498-507 of APC, codons 1304-1306 of PIK3CA. 311, codons 1450-1459 of APC, codons 856-868 of EGFR, codons 591-602 of BRAF, codons 51-58 of CDKN2A, codons 76-88 of CDKN2A, codons 90-98 of PTEN, codons 125-132 of PTEN, codons 133-146 of PTEN, codons 145-154 of PTEN, codons 250-256 of FGFR2, codons 7-19 of HRAS, codons 7-14 of KRAS, codons 57-65 of KRAS, codons 143-148 of KRAS, codons 16-18 of AKT1, T Codons 10-22 of P53, codons 25-32 of TP53, codons 33-40 of TP53, codons 40-52 of TP53, codons 52-64 of TP53, codons 82-94 of TP53, codons 97-110 of TP53, codons 112-125 of TP53, codons 123-125 of TP53, codons 126-132 of TP53, codons 132-142 of TP53, codons 150-163 of TP53, codons 167-177 of TP53, codons 175-186 of TP53, codons 187-195 of TP53, codons 195-206, codons 207-219 of TP53, codons 219-224 of TP53, codons 226-237 of TP53, codons 232-245 of TP53, codons 248-261 of TP53, codons 261-268 of TP53, codons 272-283 of TP53, codons 279-290 of TP53, codons 298-307 of TP53, codons 307-314 of TP53, codons 323-331 of TP53, codons 333-344 of TP53, codons 344-355 of TP53, codons 367-375 of TP53, and codons 374–386 of TP53, codons 175–187 of PPP2R1A, and codons 199–208 of GNAS; as well as b) tools for detecting plasma sample concentration levels of CA19-9, CEA, HGF, OPN, CA125, prolactin, TIMP-1, IL-6, myeloperoxidase, and midkine; Used to assess the presence or absence of at least two cancer types selected from the group consisting of liver cancer, ovarian cancer, esophageal cancer, gastric cancer, pancreatic cancer, colorectal cancer, lung cancer, and breast cancer in a human subject.
2. The kit of claim 1, wherein the at least two cancer types comprise at least 3, 4, 5, 6, 7 or 8 cancer types.
3. The kit of claim 1, wherein the means for detecting the plasma protein concentration is selected from the group consisting of: antibody-dependent methods (e.g., enzyme-linked immunosorbent assay (ELISA), protein immunoprecipitation, immunoelectrophoresis, western blotting, and protein immunostaining), spectroscopic methods (e.g., high performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC / MS)), and aptamer-dependent methods.
4. The kit of any one of claims 1 to 3, wherein the portions of the first and second primer pairs that are complementary to a gene or a gene portion comprise 10 to 100 nucleotides.
5. The kit of any one of claims 1 to 4, wherein the first primer pair comprises a second portion comprising a site for hybridization with a third primer.
6. The kit of any one of claims 1 to 5, wherein the second primer comprises a second portion comprising a site for hybridization with a fourth primer.
7. The kit of claim 6, wherein between the first part and the second part of the second primer is a third part consisting of 2 to 4000 nucleotides forming a unique identifier (UID).
8. Use of a reagent for evaluating a human plasma sample for preparing a kit for identifying the presence or absence of at least two types of cancer, the reagent comprising: a) a set of 61 primer pairs, wherein each primer pair comprises a first primer and a second primer, wherein the first primer and the second primer each comprise a portion complementary to a gene or a gene portion selected from the group consisting of NRAS, CTNNB1, PIK3CA, FBXW7, APC, EGFR, BRAF, CDKN2A, PTEN, FGFR2, HRAS, KRAS, AKT1, TP53, PPP2R1A and GNAS, The set of 61 primer pairs amplifies each of the following codons: codons 3-15 of NRAS, codons 54-63 of NRAS, codons 31-39 of CTNNB1, codons 38-47 of CTNNB1, codons 80-90 of PIK3CA, codons 343-348 of PIK3CA, codons 541-551 of PIK3CA, codons 1038-1050 of PIK3CA, codons 361-371 of FBXW7, codons 464-473 of FBXW7, codons 473-483 of FBXW7, codons 498-507 of APC, codons 1304-1306 of PIK3CA. 311, codons 1450-1459 of APC, codons 856-868 of EGFR, codons 591-602 of BRAF, codons 51-58 of CDKN2A, codons 76-88 of CDKN2A, codons 90-98 of PTEN, codons 125-132 of PTEN, codons 133-146 of PTEN, codons 145-154 of PTEN, codons 250-256 of FGFR2, codons 7-19 of HRAS, codons 7-14 of KRAS, codons 57-65 of KRAS, codons 143-148 of KRAS, codons 16-18 of AKT1, T Codons 10-22 of P53, codons 25-32 of TP53, codons 33-40 of TP53, codons 40-52 of TP53, codons 52-64 of TP53, codons 82-94 of TP53, codons 97-110 of TP53, codons 112-125 of TP53, codons 123-125 of TP53, codons 126-132 of TP53, codons 132-142 of TP53, codons 150-163 of TP53, codons 167-177 of TP53, codons 175-186 of TP53, codons 187-195 of TP53, codons 195-206, codons 207-219 of TP53, codons 219-224 of TP53, codons 226-237 of TP53, codons 232-245 of TP53, codons 248-261 of TP53, codons 261-268 of TP53, codons 272-283 of TP53, codons 279-290 of TP53, codons 298-307 of TP53, codons 307-314 of TP53, codons 323-331 of TP53, codons 333-344 of TP53, codons 344-355 of TP53, codons 367-375 of TP53, and codons 374–386 of TP53, codons 175–187 of PPP2R1A, and codons 199–208 of GNAS; as well as b) tools for detecting plasma sample concentration levels of CA19-9, CEA, HGF, OPN, CA125, prolactin, TIMP-1, IL-6, myeloperoxidase, and midkine; The at least two cancer types are selected from the group consisting of liver cancer, ovarian cancer, esophageal cancer, gastric cancer, pancreatic cancer, colorectal cancer, lung cancer and breast cancer.
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