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Exploration of Reduced Mitochondrial Content–Associated Gene Signature and Immunocyte Infiltration in Colon Adenocarcinoma by an Integrated Bioinformatic Analysis
Purpose: Mitochondrial dysfunction refers to cancer immune evasion. A novel 7-gene prognostic signature related to the mitochondrial DNA copy number was utilized to evaluate the immunocyte infiltration in colon cancer according to the risk scores and to predict the survival for colon cancer. Experim...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9024084/ https://www.ncbi.nlm.nih.gov/pubmed/35464857 http://dx.doi.org/10.3389/fgene.2022.832331 |
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author | Kang, Jinlin li, Na Wang, Fen Wei, Yan Zeng, Yangyang Luo, Qifan Sun, Xuehua Xu, Hui Peng, Jin Zhou, Fuxiang |
author_facet | Kang, Jinlin li, Na Wang, Fen Wei, Yan Zeng, Yangyang Luo, Qifan Sun, Xuehua Xu, Hui Peng, Jin Zhou, Fuxiang |
author_sort | Kang, Jinlin |
collection | PubMed |
description | Purpose: Mitochondrial dysfunction refers to cancer immune evasion. A novel 7-gene prognostic signature related to the mitochondrial DNA copy number was utilized to evaluate the immunocyte infiltration in colon cancer according to the risk scores and to predict the survival for colon cancer. Experimental design: We performed an integrated bioinformatic analysis to analyze transcriptome profiling of the EB-treated mitochondrial DNA–defected NCM460 cell line with differentially expressed genes between tumor and normal tissues of COAD in TCGA. The LASSO analysis was utilized to establish a prognostic signature. ESTIMATE and CIBERSORT validated the differences of immunocyte infiltration between colon cancer patients with high- and low-risk scores. Results: Our study identified a 7-gene prognostic signature (LRRN2, ANKLE1, GPRASP1, PRAME, TCF7L1, RAB6B, and CALB2). Patients with colon cancer were split into the high- and low-risk group by the risk scores in TCGA (training cohort: HR = 2.50 p < 0.0001) and GSE39582 (validation cohort: HR = 1.43 p < 0.05). ESTIMATE and CIBERSORT revealed diverseness of immune infiltration in the two groups, especially downregulated T-cell infiltration in the patients with high-risk scores. Finally, we validated the colon patients with a low expression of the mitochondrial number biomarker TFAM had less CD3(+) and CD8(+) T-cell infiltration in clinical specimens. Conclusion: An mtDNA copy number-related 7-gene prognostic signature was investigated and evaluated, which may help to predict the prognosis of colon cancer patients and to guide clinical immunotherapy via immunocyte infiltration evaluation. |
format | Online Article Text |
id | pubmed-9024084 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90240842022-04-23 Exploration of Reduced Mitochondrial Content–Associated Gene Signature and Immunocyte Infiltration in Colon Adenocarcinoma by an Integrated Bioinformatic Analysis Kang, Jinlin li, Na Wang, Fen Wei, Yan Zeng, Yangyang Luo, Qifan Sun, Xuehua Xu, Hui Peng, Jin Zhou, Fuxiang Front Genet Genetics Purpose: Mitochondrial dysfunction refers to cancer immune evasion. A novel 7-gene prognostic signature related to the mitochondrial DNA copy number was utilized to evaluate the immunocyte infiltration in colon cancer according to the risk scores and to predict the survival for colon cancer. Experimental design: We performed an integrated bioinformatic analysis to analyze transcriptome profiling of the EB-treated mitochondrial DNA–defected NCM460 cell line with differentially expressed genes between tumor and normal tissues of COAD in TCGA. The LASSO analysis was utilized to establish a prognostic signature. ESTIMATE and CIBERSORT validated the differences of immunocyte infiltration between colon cancer patients with high- and low-risk scores. Results: Our study identified a 7-gene prognostic signature (LRRN2, ANKLE1, GPRASP1, PRAME, TCF7L1, RAB6B, and CALB2). Patients with colon cancer were split into the high- and low-risk group by the risk scores in TCGA (training cohort: HR = 2.50 p < 0.0001) and GSE39582 (validation cohort: HR = 1.43 p < 0.05). ESTIMATE and CIBERSORT revealed diverseness of immune infiltration in the two groups, especially downregulated T-cell infiltration in the patients with high-risk scores. Finally, we validated the colon patients with a low expression of the mitochondrial number biomarker TFAM had less CD3(+) and CD8(+) T-cell infiltration in clinical specimens. Conclusion: An mtDNA copy number-related 7-gene prognostic signature was investigated and evaluated, which may help to predict the prognosis of colon cancer patients and to guide clinical immunotherapy via immunocyte infiltration evaluation. Frontiers Media S.A. 2022-04-08 /pmc/articles/PMC9024084/ /pubmed/35464857 http://dx.doi.org/10.3389/fgene.2022.832331 Text en Copyright © 2022 Kang, li, Wang, Wei, Zeng, Luo, Sun, Xu, Peng and Zhou. 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 | Genetics Kang, Jinlin li, Na Wang, Fen Wei, Yan Zeng, Yangyang Luo, Qifan Sun, Xuehua Xu, Hui Peng, Jin Zhou, Fuxiang Exploration of Reduced Mitochondrial Content–Associated Gene Signature and Immunocyte Infiltration in Colon Adenocarcinoma by an Integrated Bioinformatic Analysis |
title | Exploration of Reduced Mitochondrial Content–Associated Gene Signature and Immunocyte Infiltration in Colon Adenocarcinoma by an Integrated Bioinformatic Analysis |
title_full | Exploration of Reduced Mitochondrial Content–Associated Gene Signature and Immunocyte Infiltration in Colon Adenocarcinoma by an Integrated Bioinformatic Analysis |
title_fullStr | Exploration of Reduced Mitochondrial Content–Associated Gene Signature and Immunocyte Infiltration in Colon Adenocarcinoma by an Integrated Bioinformatic Analysis |
title_full_unstemmed | Exploration of Reduced Mitochondrial Content–Associated Gene Signature and Immunocyte Infiltration in Colon Adenocarcinoma by an Integrated Bioinformatic Analysis |
title_short | Exploration of Reduced Mitochondrial Content–Associated Gene Signature and Immunocyte Infiltration in Colon Adenocarcinoma by an Integrated Bioinformatic Analysis |
title_sort | exploration of reduced mitochondrial content–associated gene signature and immunocyte infiltration in colon adenocarcinoma by an integrated bioinformatic analysis |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9024084/ https://www.ncbi.nlm.nih.gov/pubmed/35464857 http://dx.doi.org/10.3389/fgene.2022.832331 |
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