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Identification of cuproptosis -related subtypes, the development of a prognosis model, and characterization of tumor microenvironment infiltration in prostate cancer
Cuproptosis, Copper Induced Cell Death, is a newly defined type of programmed cell death, involving in the regulation of tricarboxylic acid (TCA) cycle. Dysfunction of cuproptosis induces cytotoxicity and influences the proliferation of multiple tumors. However, the direct prognostic effect of cupro...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9530990/ https://www.ncbi.nlm.nih.gov/pubmed/36203594 http://dx.doi.org/10.3389/fimmu.2022.974034 |
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author | Jin, Liang Mei, Wangli Liu, Xiang Sun, Xianchao Xin, Shiyong Zhou, Zhen Zhang, Jiaxin Zhang, Bihui Chen, Ping Cai, Ming Ye, Lin |
author_facet | Jin, Liang Mei, Wangli Liu, Xiang Sun, Xianchao Xin, Shiyong Zhou, Zhen Zhang, Jiaxin Zhang, Bihui Chen, Ping Cai, Ming Ye, Lin |
author_sort | Jin, Liang |
collection | PubMed |
description | Cuproptosis, Copper Induced Cell Death, is a newly defined type of programmed cell death, involving in the regulation of tricarboxylic acid (TCA) cycle. Dysfunction of cuproptosis induces cytotoxicity and influences the proliferation of multiple tumors. However, the direct prognostic effect of cuproptosis related genes and corresponding regulating mechanisms amid prostate cancer remains unknown. A multi-omics analysis strategy was adopted to explore the role of ten cuproptosis related genes in The Cancer Genome Atlas- Prostate Adenocarcinoma (TCGA-PRAD). Firstly, mRNA expression, Copy Number Variance (CNV), mutation, DNA methylation and prognostic power of the ten genes were illustrated. Based on transcriptomic data, we developed a novel prognostic model named the Cuproptosis-related gene score (CRGScore), Their biological functions were then detected by enrichment analysis and unsupervised cluster analysis. Following that, their correlation with Tumor Immune Microenvironment (TIME), immunotherapy, Biochemical Recurrence (BCR) and chemotherapeutic resistance were elaborated by relevant bioinformatics algorithms. Ten cuproptosis related genes exhibited extensive alteration of CNV and DNA methylation and showed significant influence on the prognosis of prostate cancer patients. These genes mainly enriched in E2F and G2M targets and mitosis pathways, Samples with high CRGScore showed enhancement resulting in the increased infiltration of T cell, B cell, NK cells. They also demonstrated close correlations with the BCR status, expression of eight immune checkpoints and chemotherapeutic resistances in prostate cancer. Our comprehensive analysis of CRGScore revealed an extensive regulatory mechanism by which they affect the tumor-immune-stromal microenvironment, clinicopathological features, and prognosis. We also determined the therapeutic liability of CRGScore in targeted therapy and immunotherapy. These findings highlight the crucial clinical implications of CRGScore and provide new ideas for guiding personalized immunotherapy strategies for patients with Pca. |
format | Online Article Text |
id | pubmed-9530990 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95309902022-10-05 Identification of cuproptosis -related subtypes, the development of a prognosis model, and characterization of tumor microenvironment infiltration in prostate cancer Jin, Liang Mei, Wangli Liu, Xiang Sun, Xianchao Xin, Shiyong Zhou, Zhen Zhang, Jiaxin Zhang, Bihui Chen, Ping Cai, Ming Ye, Lin Front Immunol Immunology Cuproptosis, Copper Induced Cell Death, is a newly defined type of programmed cell death, involving in the regulation of tricarboxylic acid (TCA) cycle. Dysfunction of cuproptosis induces cytotoxicity and influences the proliferation of multiple tumors. However, the direct prognostic effect of cuproptosis related genes and corresponding regulating mechanisms amid prostate cancer remains unknown. A multi-omics analysis strategy was adopted to explore the role of ten cuproptosis related genes in The Cancer Genome Atlas- Prostate Adenocarcinoma (TCGA-PRAD). Firstly, mRNA expression, Copy Number Variance (CNV), mutation, DNA methylation and prognostic power of the ten genes were illustrated. Based on transcriptomic data, we developed a novel prognostic model named the Cuproptosis-related gene score (CRGScore), Their biological functions were then detected by enrichment analysis and unsupervised cluster analysis. Following that, their correlation with Tumor Immune Microenvironment (TIME), immunotherapy, Biochemical Recurrence (BCR) and chemotherapeutic resistance were elaborated by relevant bioinformatics algorithms. Ten cuproptosis related genes exhibited extensive alteration of CNV and DNA methylation and showed significant influence on the prognosis of prostate cancer patients. These genes mainly enriched in E2F and G2M targets and mitosis pathways, Samples with high CRGScore showed enhancement resulting in the increased infiltration of T cell, B cell, NK cells. They also demonstrated close correlations with the BCR status, expression of eight immune checkpoints and chemotherapeutic resistances in prostate cancer. Our comprehensive analysis of CRGScore revealed an extensive regulatory mechanism by which they affect the tumor-immune-stromal microenvironment, clinicopathological features, and prognosis. We also determined the therapeutic liability of CRGScore in targeted therapy and immunotherapy. These findings highlight the crucial clinical implications of CRGScore and provide new ideas for guiding personalized immunotherapy strategies for patients with Pca. Frontiers Media S.A. 2022-09-20 /pmc/articles/PMC9530990/ /pubmed/36203594 http://dx.doi.org/10.3389/fimmu.2022.974034 Text en Copyright © 2022 Jin, Mei, Liu, Sun, Xin, Zhou, Zhang, Zhang, Chen, Cai and Ye https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Jin, Liang Mei, Wangli Liu, Xiang Sun, Xianchao Xin, Shiyong Zhou, Zhen Zhang, Jiaxin Zhang, Bihui Chen, Ping Cai, Ming Ye, Lin Identification of cuproptosis -related subtypes, the development of a prognosis model, and characterization of tumor microenvironment infiltration in prostate cancer |
title | Identification of cuproptosis -related subtypes, the development of a prognosis model, and characterization of tumor microenvironment infiltration in prostate cancer |
title_full | Identification of cuproptosis -related subtypes, the development of a prognosis model, and characterization of tumor microenvironment infiltration in prostate cancer |
title_fullStr | Identification of cuproptosis -related subtypes, the development of a prognosis model, and characterization of tumor microenvironment infiltration in prostate cancer |
title_full_unstemmed | Identification of cuproptosis -related subtypes, the development of a prognosis model, and characterization of tumor microenvironment infiltration in prostate cancer |
title_short | Identification of cuproptosis -related subtypes, the development of a prognosis model, and characterization of tumor microenvironment infiltration in prostate cancer |
title_sort | identification of cuproptosis -related subtypes, the development of a prognosis model, and characterization of tumor microenvironment infiltration in prostate cancer |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9530990/ https://www.ncbi.nlm.nih.gov/pubmed/36203594 http://dx.doi.org/10.3389/fimmu.2022.974034 |
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