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Potential antigen obviously related to prognosis of renal clear cell carcinoma, immune subtype and construction method and application of potential antigen and immune subtype

A technique for renal clear cell carcinoma and immunophenotyping, which is applied in the field of renal clear cell carcinoma prediction and vaccine development, and can solve problems such as research lag and unsatisfactory results

Pending Publication Date: 2022-03-11
WEST CHINA HOSPITAL SICHUAN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

mRNA vaccine is a kind of immunotherapy, which was proposed as a promising anti-tumor method 20 years ago. However, the research of mRNA vaccine in KIRC lags behind slightly, and the effect in clinical trials is still unsatisfactory

Method used

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  • Potential antigen obviously related to prognosis of renal clear cell carcinoma, immune subtype and construction method and application of potential antigen and immune subtype
  • Potential antigen obviously related to prognosis of renal clear cell carcinoma, immune subtype and construction method and application of potential antigen and immune subtype
  • Potential antigen obviously related to prognosis of renal clear cell carcinoma, immune subtype and construction method and application of potential antigen and immune subtype

Examples

Experimental program
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Effect test

Embodiment 1

[0057] Example 1 provides a potential antigen significantly related to the prognosis of clear cell renal cell carcinoma. The specific screening process is as follows:

[0058] 1.1 The expression profile data of clear cell renal cell carcinoma were obtained as follows:

[0059] KIRC expression profile:

[0060] https: / / gdc-hub.s3.us-east-1.amazonaws.com / download / TCGA-KIRC.htseq_fpkm.tsv.gz.

[0061] KIRC phenotype data:

[0062] https: / / gdc-hub.s3.us-east-1.amazonaws.com / download / TCGA-KIRC.GDC_phenotype.tsv.gz.

[0063] KIRC Survival Data:

[0064] https: / / gdc-hub.s3.us-east-1.amazonaws.com / download / TCGA-KIRC.survival.tsv.

[0065] Table 1 shows the clinical information of 589 samples from TCGA-KIRC, as shown in Table 1. Table 2 shows the clinical information of TCGA-KIRC518 cancer samples, as follows.

[0066] Table 1 Clinical information of 589 samples from TCGA-KIRC

[0067]

[0068] Table 2 Clinical information of 518 cancer samples from TCGA-KIRC

[0069]

[...

Embodiment 2

[0097] This embodiment 2 provides an immunophenotyping related to renal clear cell carcinoma, and the specific construction process is as follows:

[0098] 2.1 Identification of potential immune subtypes.

[0099] Immunophenotyping can be used to reflect the immune status of the tumor and its microenvironment, thereby helping to identify patients suitable for vaccination. Therefore, the present invention constructs consensus clustering by analyzing the expression profiles of 1621 immune-related genes in KIRC cancer samples. According to its cumulative distribution function and incremental area plot, k=2 is selected for stable clustering of immune-related genes (eg Image 6 A-6C), two immune subtypes were obtained, named cluster1 and cluster2 respectively. Then, the two subtypes were verified by principal component analysis, and the results showed that the two subtypes could also be distinguished well (such as Image 6 D). Simultaneously, the present invention also shows th...

Embodiment 3

[0114] This embodiment 3 provides a method of using immunophenotyping to predict the therapeutic effect of clear cell renal cell carcinoma vaccines on patients with clear cell renal cell carcinoma. Prognostic risk score, and according to the median risk score, immune subtypes were divided into high and low risk groups.

[0115] Preferably, the construction process of the prognostic scoring model includes:

[0116] Method 1: Identification of KIRC immune gene co-expression module and prognosis module.

[0117] The immune gene co-expression module clusters samples through WGCNA (such as Figure 15 A), the scale-free network soft threshold is 3 (such as Figure 15 B). The expression matrix is ​​then converted to an adjacency matrix and then to a topology matrix. Using the default parameters of the "WGCNA" R package, 10 modules were finally obtained, and the gray modules were not gathered together (such as Figure 15 C). Figure 15 D shows the number of genes in each module....

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Abstract

The invention provides a potential antigen obviously related to prognosis of renal clear cell carcinoma, an immune subtype and a construction method and application thereof, and the potential antigen comprises one or more of the following antigen genes: ZAP70, VMP1, TUBB6, TPX2, TOP2A, TMEM74B, TMC8, TGM2, TGFA, TEX11, SPON2, SNX33, SERPINH1, RUNX1, RRM2, RGCC, PTTG1, PTP4A3, PPP1R18, PLAUR, PABPC1L, NCF4, MYBL2, MUC3A, MSC, MGARP, FOXM1, FMNL1, FBXL16, EDN1, DOK3, COL5A3, CDHR5, according to the invention, a new tumor antigen of renal clear cell carcinoma is explored to be suitable for research and development of mRNA vaccine of KIRC; besides, the invention also identifies the immune typing of the KIRC, so that the immune typing is used for predicting the treatment effect of the renal clear cell carcinoma vaccine prepared based on potential antigens significantly related to renal clear cell carcinoma prognosis on renal clear cell carcinoma patients, and a new thought is provided for developing mRNA vaccines of the KIRC and identifying KIRC patients suitable for mRNA vaccination.

Description

technical field [0001] The present invention relates to the technical field of renal clear cell carcinoma prediction and vaccine development, in particular to a potential antigen significantly related to the prognosis of renal clear cell carcinoma, immune typing and its construction typing and application. Background technique [0002] mRNA vaccines have emerged as a promising platform for cancer immunotherapy, and with the recent approval of two mRNA-LNP vaccines for the prevention of COVID-19, mRNA vaccines are undergoing preclinical and clinical research in the fields of cancer and infectious diseases. With rapid development. Compared with infectious disease vaccines, the challenges in developing cancer vaccines are: Although anticancer preventive vaccines are still in preclinical research, clinical applications are limited due to antigenic prediction difficulties and poor immunogenicity; effective anticancer vaccines Another major hurdle in development is the identifica...

Claims

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Application Information

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IPC IPC(8): C12Q1/6886A61K39/00A61P35/00A61P13/12G16B25/00G16B20/50G16B40/00
CPCC12Q1/6886A61K39/0011A61P35/00A61P13/12G16B25/00G16B20/50G16B40/00C12Q2600/118C12Q2600/106C12Q2600/158C12Q2600/156A61K2039/868A61K2039/53
Inventor 艾建忠郑筱男曹德宏徐航易贤彦翎张天燚李晋
Owner WEST CHINA HOSPITAL SICHUAN UNIV
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