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Application of COPA in preparation of cervical cancer diagnosis biomarker and/or development of cervical cancer drugs

A biomarker, cervical cancer technology, applied in biochemical equipment and methods, microbial determination/examination, drug combination, etc., can solve the problem of cervical cancer without early diagnosis and prognosis judgment methods, etc., to promote clinical transformation Effect

Active Publication Date: 2022-04-26
GUANGDONG GENERAL HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, there is no biomarker-based method for early diagnosis and prognosis of cervical cancer

Method used

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  • Application of COPA in preparation of cervical cancer diagnosis biomarker and/or development of cervical cancer drugs
  • Application of COPA in preparation of cervical cancer diagnosis biomarker and/or development of cervical cancer drugs
  • Application of COPA in preparation of cervical cancer diagnosis biomarker and/or development of cervical cancer drugs

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Based on the non-targeted quantitative proteomics of LC-MS / MS, a comprehensive proteomic analysis of cervical cancer is carried out, and a candidate biomarker COPA of cervical cancer is screened out, including the following steps:

[0033] (1) Randomly select patients who were treated in the Department of Gynecology of Guangdong Provincial People's Hospital from January 1, 2020 to May 31, 2020, and underwent surgical treatment for cervical cancer, and patients who were treated in the Department of Gynecology of Guangdong Provincial People's Hospital during the same period, and underwent surgery for uterine leiomyoma Hysterectomy patients were used as controls (preoperative cervical liquid-based thin-layer cytology examination and high-risk human papillomavirus DNA detection were negative). AC represents the cervical adenocarcinoma group, SCC represents the cervical squamous cell carcinoma group, and H represents the normal cervical control group (n=11 in the AC group, n=...

Embodiment 2

[0037] PRM-based targeted quantitative proteomics validation of COPA as a biomarker of cervical cancer, including the following analysis steps:

[0038] PRM-based targeted quantitative proteomics based on GITGVDLFGTTDAVVK and CPLSGACYSPEFK unique peptide targets in an additional 45 surgically collected fresh-frozen tissue samples (n=19 for AC group, n=18 for SCC group, n=8 for H group) COPA was quantified. By comparing the expression levels of COPA protein in the three groups, we found that: the expression level of COPA in the AC group was significantly increased by 2.8 times compared with that in the H group (P=0.000253), and the expression level of COPA in the SCC group was significantly higher than that in the H group. Up-regulated by 2.07 times (P=0.004), the expression level of COPA in the AC group was significantly up-regulated by 1.35 times compared with the SCC group (P=0.0295), indicating that COPA can not only be used as a biomarker for cervical cancer, but also for ...

Embodiment 3

[0041] The proteomic results were verified again by IHC in a large number of cervical cancer samples, and the relationship between the IHC staining intensity of COPA in cervical cancer tissues and the FIGO stage of patients was analyzed, including the following analysis steps:

[0042] (1) Paraffin wax samples of tumor tissues from the collection of cervical cancer: Randomly select paraffin wax samples of cervical cancer tissues from the Department of Pathology, Guangdong Provincial People’s Hospital from January 1, 2015 to December 31, 2020 (n=85 in AC group, n=85 in SCC group) n=55), cut into thin slices with a thickness of 5 μm, stick them on glass slides, put them into slice bleaching temperature controller and bake the slices for 15-30 minutes.

[0043] (2) COPA immunohistochemical staining: The rabbit COPA monoclonal antibody used in COPA immunohistochemical staining was purchased from Abcam (Cat. No. ab181224), and the antibody concentration was 1:100. Co., Ltd.) instru...

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Abstract

The invention discloses application of COPA in preparation of a cervical cancer diagnosis biomarker and / or development of cervical cancer drugs. Based on a comprehensive proteomics analysis strategy (combining non-targeted proteomics based on LC-MS with targeted proteomics based on PRM), the COPA is identified as the biological marker of cervical cancer for the first time, and is verified again through IHC staining; in addition, the COPA staining intensity in the tumor tissue is related to the FIGO staging of a patient, and the prognosis of a person with moderate-strong positive COPA staining is poor. The COPA is applied to preparation of the cervical cancer diagnosis biomarker, and patients can be accurately classified. The inventor also observes that targeting down-regulation of COPA protein in cervical cancer cells significantly inhibits invasiveness of cancer cells for the first time, and determines that COPA is an intervention target of cervical cancer. The COPA is applied to development of cervical cancer drugs, molecular targeted therapy is carried out on high-risk patients, and prognosis can be improved.

Description

technical field [0001] The invention belongs to the field of medical biotechnology, and particularly relates to the application of COPA in the preparation of cervical cancer diagnostic biomarkers and / or the development of cervical cancer drugs. Background technique [0002] Cervical cancer is the fourth most common gynecological tumor in the world, and it ranks second among common tumors among women aged 20-39. Cervical adenocarcinoma (Adenocarcinoma, AC) and cervical squamous cell carcinoma (Squamous cellcarcinoma, SCC) are two main pathological types of cervical cancer. According to data released by the World Health Organization's International Agency for Research on Cancer (IARC), the number of new cases of cervical cancer in the world in 2020 is about 600,000, and the number of deaths is about 340,000. Among them, the number of new cases of cervical cancer in my country is about 110,000, and the death toll is about 60,000, ranking first in gynecological tumors. Although...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886G01N33/574A61K45/00A61P35/00
CPCC12Q1/6886G01N33/57411G01N33/57484A61K45/00A61P35/00C12Q2600/158C12Q2600/136G01N2333/47G01N2500/04Y02A50/30
Inventor 包慧琼黄志宏梅平
Owner GUANGDONG GENERAL HOSPITAL