CN-121617483-B - Molecular classification diagnosis system for diagnosing prostate cancer through multi-target combined weight system

CN121617483BCN 121617483 BCN121617483 BCN 121617483BCN-121617483-B

Abstract

The invention discloses a molecular classification diagnosis system for diagnosing prostate cancer through a multi-target combined weight system, and belongs to the technical field of biological medicines. The method comprises the steps of establishing a weight diagnosis formula for classifying prostate cancer and benign hyperplasia of the prostate by utilizing an existing clinical database containing information of patients with prostate cancer and benign hyperplasia, establishing a mathematical logic relation among multiple targets through data training, namely, weight proportion of 4 prostate cancer related biomarkers to prostate cancer diagnosis, establishing a weight detection system, taking a DNA tetrahedron framework nucleic acid dimer structure as a signal output substrate, and constructing a multi-target combined intelligent diagnosis system by pricing and modifying different signal molecules on a signal output probe, so that the accurate classification of the prostate cancer and benign hyperplasia of the prostate is realized, and the accuracy of early diagnosis of the prostate cancer is improved.

Inventors

ZUO XIAOLEI
FAN CHUNHAI
XUE WEI
ZHANG SHUYANG
DONG BAIJUN
Tao Hanyang

Assignees

上海交通大学医学院附属仁济医院

Dates

Publication Date: 20260512
Application Date: 20260130

Claims (9)

1. A molecular classification diagnosis system for diagnosing prostate cancer through a multi-target combined weight system comprises a data acquisition module and an analysis module, and is characterized in that: The data acquisition module comprises a protein acquisition unit and a fluorescence detection unit, wherein the protein acquisition unit is used for acquiring 4 biomarkers related to prostate cancer in a sample to be detected, the 4 biomarkers are respectively Cyclin-dependent kinase (Cyclin-DEPENDENT KINASE, CDK 12), golgi membrane protein 1 (Golgi membrane protein 1, GOLM 1), outer nucleotide triphosphatehydrolase 5 (Ectonucleoside triphosphate diphosphohydrolase 5, ENTPD 5) and growth differentiation factor 15 (Growth differentiating factor, GDF 15), and the fluorescence detection unit is used for performing fluorescence imaging and quantification on the biomarkers and outputting the biomarkers to the analysis module; The analysis module is used for analyzing the fluorescence imaging and quantitative results and classifying the prostate cancer and benign hyperplasia of the prostate through a weight diagnosis formula, wherein the weight diagnosis formula is as follows: diagnostic value r=q1 fluorescence intensity CDK12 +q2 fluorescence intensity GOLM1 +q3 fluorescence intensity ENTPD5 +q4 fluorescence intensity GDF15 ; Wherein Q1, Q2, Q3, Q4 are the weights of CDK12, GOLM1, ENTPD5, GDF15, respectively, Q1++4, Q2= -1, Q3= +1, Q4= +2; The data acquisition module synthesizes the biomarker, the capture antibody, the detection antibody, the biotin-modified secondary antibody and the fluorescent group-modified DNA tetrahedral framework nucleic acid into a DNA tetrahedral framework nucleic acid dimer structure, and performs fluorescent scanning on the DNA tetrahedral framework nucleic acid dimer structure to realize fluorescent imaging and quantification of the biomarker; The number of the fluorescent groups modified by the DNA tetrahedral framework nucleic acid is consistent with the weight of the biomarker, and the DNA tetrahedral framework nucleic acid is formed by self-assembly of 4 single-stranded DNA selected from the sequences SEQ ID No. 1-9.
2. The molecular classification diagnostic system for diagnosing prostate cancer via a multi-target combined weighting system of claim 1, wherein said process of capturing said biomarker and performing fluorescence detection by said data acquisition module comprises the steps of: s1, preparing a capture antibody on a gold island substrate, incubating overnight in a wet box, keeping antibody droplets wet, and constructing a protein capture interface; S2, sealing a protein capture interface; S3, incubating serum of a patient; s4, incubating the detection antibody; S5, incubating a secondary antibody of modified biotin; S6, incubating streptavidin; s7, synthesizing and incubating a DNA tetrahedral framework nucleic acid dimer structure modified by biotin and a fluorescent group; s8, washing the capture interface with pure water, and centrifuging to completely dry the interface; s9, performing fluorescence imaging and quantification on the protein capture interface by using a chip scanner.
3. The molecular classification diagnostic system for diagnosing prostate cancer by a multi-target combined weight system according to claim 2, wherein the concentration of the capture antibody in step S1 is 2 μm and the humidity in the wet box is 65% -75%.
4. The molecular classification diagnostic system for diagnosing prostate cancer by a multi-target combined weight system of claim 2, wherein in step S2, the blocking agent is 2% bovine serum albumin and the blocking time is 1 hour.
5. The molecular classification diagnostic system for diagnosing prostate cancer by a multi-target combined weighting system of claim 2, wherein in step S3, the patient serum incubation time is 2.5 hours.
6. The molecular classification diagnostic system for diagnosing prostate cancer by a multi-target combined weight system according to claim 2, wherein the concentration of the detection antibody in step S4 is 50nM and the incubation time is 1.5 hours.
7. The molecular classification diagnostic system for diagnosing prostate cancer by a multi-target combined weight system according to claim 2, wherein the modified biotin has a secondary antibody concentration of 20 nM and an incubation time of 20 minutes in step S5.
8. The molecular classification diagnostic system for diagnosing prostate cancer by a multi-target combined weight system according to claim 2, wherein the concentration of streptavidin in step S6 is 50 nM and the incubation time is 1 hour.
9. The molecular classification diagnostic system for diagnosing prostate cancer by a multi-target combined weight system of claim 2, wherein the incubation time is 1 hour in step S11.

Description

Molecular classification diagnosis system for diagnosing prostate cancer through multi-target combined weight system Technical Field The invention relates to the technical field of biological medicine, in particular to a molecular classification diagnosis system for diagnosing prostate cancer through a multi-target combined weight system. Background Cancer is one of the most interesting disease types in the world of medical health today, the most deadly disease type today, and its incidence is on a rapid annual increasing trend worldwide. Through decades of researches on the occurrence and evolution mechanism of cancer, the medical community has clarified the concept of preventive and therapeutic treatment of the cancer, namely, the diagnosis and treatment time of the cancer is advanced, the early screening and early intervention of the cancer course are enhanced, and the method becomes consensus for improving the cure efficiency and/or effectively inhibiting the tumor growth. The progression of cancer is diverse, and the progression of disease involves multiple key molecular events, so single target diagnosis is often less accurate. Taking prostate cancer as an example, clinically, PSA protein in serum is mainly detected at present, and suspected patients are primarily screened. However, the detection method has low accuracy and is mainly characterized in that (1) the false positive rate is high, namely, even healthy people and benign prostatic hyperplasia patients possibly have slightly raised PSA (the accuracy of clinical diagnosis in the tumor stage I is only 10 percent and the clinical diagnosis in the tumor stage II is only 24 percent), and the crowd to be detected is faced with the choice of whether to carry out the next detailed examination (such as prostate puncture). (2) For patients who have been diagnosed with prostate cancer, there is no clear relationship between the level of PSA and tumor size. The PSA content may vary widely from patient to patient even though the tumors are similar in size, PSA may continue to rise for the same prostate cancer patient with reduced tumor size after treatment, and PSA may instead decrease as treatment-ineffective tumors continue to grow. Since a single biomarker cannot provide multiple biological level information of a tumor, multi-target combinatorial analysis becomes a key to improving diagnostic accuracy from different biological information. Therefore, the establishment of a uniform and universal chemical measurement method of the markers and the establishment of a multi-target combined diagnosis system are key to improving the diagnosis accuracy. The invention provides a molecular classification diagnosis system for diagnosing prostate cancer through a multi-target combined weight system, so as to realize highly accurate diagnosis of the prostate cancer. Disclosure of Invention Aiming at the defects in the prior art, the invention provides a molecular classification diagnosis system for diagnosing prostate cancer through a multi-target combined weight system, which is used for classifying patients with abnormal PSA (pressure swing adsorption) or prostate cancer related symptoms after primary screening, and the classification of prostate cancer and benign hyperplasia of the prostate is realized by constructing a multi-target combined intelligent diagnosis system, so that the accuracy of early diagnosis of the prostate cancer is improved. In order to achieve the above purpose, the invention adopts the following technical scheme: A molecular classification diagnosis system for diagnosing prostate cancer through a multi-target combined weight system, comprising a data acquisition module and an analysis module, wherein the data acquisition module comprises a protein acquisition unit and a fluorescence detection unit, the protein acquisition unit is used for acquiring 4 biomarkers related to the prostate cancer in a sample to be tested, the 4 biomarkers are respectively Cyclin-dependent kinase (Cyclin-DEPENDENT KINASE, CDK 12), golgi membrane protein 1 (Golgi membrane protein 1, GOLM1), outer nucleotide triphosphatehydrolase 5 (Ectonucleoside triphosphate diphosphohydrolase, ENTPD 5) and growth differentiation factor 15 (Growth differentiating factor, GDF 15), and the fluorescence detection unit is used for performing fluorescence imaging and quantification on the biomarkers and outputting the biomarkers to the analysis module; The analysis module is used for analyzing the fluorescence imaging and quantitative results and classifying the prostate cancer and benign hyperplasia of the prostate through a weight diagnosis formula, wherein the weight diagnosis formula is as follows: diagnostic value r=q1 fluorescence intensity CDK12 +q2 fluorescence intensity GOLM1 +q3 fluorescence intensity ENTPD5 +q4 fluorescence intensity GDF15; Wherein Q1, Q2, Q3, Q4 are the weights of CDK12, GOLM1, ENTPD5, GDF15, respectively, Q1++4, Q2= -1, Q3= +1, Q4= +2; The data acquisitio