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Potential antigen significantly related to prostate cancer, immune subtype, construction method and application thereof

A prostate cancer and immunophenotyping technology, which is applied in the direction of antibody medical components, biochemical equipment and methods, and medical preparations containing active ingredients, can solve the problems of failing to improve the overall survival rate of patients, and achieve improved treatment and prevention effect of effect

Pending Publication Date: 2022-07-29
WEST CHINA HOSPITAL SICHUAN UNIV
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  • Abstract
  • Description
  • Claims
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AI Technical Summary

Problems solved by technology

Phase I / II clinical trials showed that CV9103 was well tolerated and immune-stimulating; did not improve the overall survival rate of patients

Method used

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  • Potential antigen significantly related to prostate cancer, immune subtype, construction method and application thereof
  • Potential antigen significantly related to prostate cancer, immune subtype, construction method and application thereof
  • Potential antigen significantly related to prostate cancer, immune subtype, construction method and application thereof

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Embodiment 1

[0059] The present embodiment 1 provides a potential antigen significantly related to the prognosis of prostate cancer, and the specific screening process is as follows:

[0060] 1.1. Differential expression analysis Identify overexpressed genes.

[0061] To identify potential antigens for the TCGA-PRAD cohort, transcriptome expression profiling data for the TCGA-PRAD cohort were first downloaded from xena (xena.ucsc.edu). The data consisted of 52 normal samples and 499 prostate cancer patients, and the PRAD cohort data were differentially analyzed using the edgeR package in R. Differential gene screening threshold was |log2FC|>1 and FDRfigure 1 A and 1B are shown, where figure 1 A is a volcano plot of differentially expressed genes, figure 1 B is a heat map of differentially expressed genes. Then use GEPIA (http: / / gepia2.cancer-pku.cn, version 2) to draw the distribution map of differentially expressed genes on genome chromosomes, such as figure 1 As shown in C, figure 1...

Embodiment 2

[0072] The present embodiment 2 provides a kind of immune typing related to prostate cancer, and the specific construction process is as follows:

[0073] 2.1. Identification of immune subtypes.

[0074] The vaccine response gene set (c7.vax.v7.4.symbols.gmt) in the c7 immune gene set was obtained by MSigDB, including 13426 immune genes. Using lasso regression analysis to screen the immune gene set related to prognosis, 22 immune genes related to prognosis were obtained, such as Image 6 As shown in E, Image 6 E is the expression heat map of immune-related genes. The prognosis-related immune genes include the following genes: PTEN, CSMD3, RORC, PLEK2, FA2H, GLB1L3, MDK, LRRC75A, RUNDC3A, VWA5B2, DHX58, ADAM11, HAGHL, KPTAP5-1, PLEKHN1, HOXC5, SLC25A29, SEC61A2, ZDHHC11B, SNORD36C, ATG9B and PLIN1. The cancer samples were then subjected to unsupervised clustering using ConsensusClusterPlus to obtain 3 immune subtypes, named C1, C2 and C3, as in Image 6 As shown in A, Im...

Embodiment 3

[0094] This embodiment provides a method for predicting the therapeutic effect of a prostate cancer vaccine on prostate cancer patients by using the immune typing of Example 2, the method comprising using a constructed prognostic scoring model for prostate cancer patients to perform a prognostic risk score on a patient sample , and divide the immune subtype into high and low risk groups with the median as the node, specifically:

[0095] 3.1. The construction process of the prognostic scoring model includes:

[0096] method one:

[0097] Step 1: Construction of WGCNA co-expression network.

[0098]Weighted co-expression network analysis was performed on genes related to prognosis in immune-related genes (c7.vax.v7.4.symbols.gmt), and after soft threshold screening, a network was constructed with power=9 ( Figure 16 A-D), then calculate the eigengenes of each module corresponding to each sample, and detect whether there are differences in the distribution of eigengenes in di...

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Abstract

The invention provides a potential antigen related to prostatic cancer, an immune subtype and a construction method and application of the potential antigen and the immune subtype. The potential antigen comprises one or more of the following antigen genes: KLHL17, CPT1B, IQGAP3, LIME1, YJEFN3, KIAA1529, MSH5 and CELSR3. The invention further discloses a preparation method of the potential antigen. According to the invention, genes up-regulated and mutated in prostatic cancer are screened, molecules with relatively strong tumor prognosis and immune infiltration correlation are found as potential mRNA vaccine antigens, and then the mRNA vaccine for treating or preventing the prostatic cancer is prepared, so that a new direction is provided for treatment and prevention of patients with the prostatic cancer. Meanwhile, the invention also provides an immune subtype related to prostatic cancer as well as a construction method and application of the immune subtype. The treatment effect of the prostate cancer vaccine prepared based on potential antigens significantly related to prostate cancer prognosis on a prostate cancer patient is predicted through immunological typing, and then the mRNA vaccine suitable for being inoculated by people is screened out.

Description

technical field [0001] The invention relates to the technical field of tumor prediction and vaccine development, in particular to a potential antigen related to prostate cancer, immune typing, and a construction method and application thereof. Background technique [0002] In recent years, with the gradual improvement of my country's living standards and the continuous prolongation of life expectancy, the incidence of prostate cancer has been increasing year by year. In the past few decades, prostate cancer treatment has been dominated by androgen deprivation therapy, surgery and chemotherapy. In recent years, immunotherapy has included CAR-T therapy and monoclonal targeting of programmed cell death protein 1 (PD-1), PD-ligand 1 (PD-L1) or cytotoxic T lymphocyte antigen 4 (CTLA-4). Antibodies have been widely developed for cancer treatment, yet prostate cancer patients have low response rates to these treatments. Previously, Sipuleucel-T was reported to prolong the surviva...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886A61K39/00A61P35/00A61P13/08G16B25/00G16B20/50G16B40/00
CPCC12Q1/6886A61K39/0011A61P35/00A61P13/08G16B25/00G16B20/50G16B40/00C12Q2600/118C12Q2600/106C12Q2600/158C12Q2600/156A61K2039/884A61K2039/53
Inventor 艾建忠郑筱男徐航易贤彦翎张天燚
Owner WEST CHINA HOSPITAL SICHUAN UNIV
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