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.Experime...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.832331/full |
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| author | Jinlin Kang Jinlin Kang Jinlin Kang Na li Na li Na li Na li Fen Wang Fen Wang Fen Wang Yan Wei Yan Wei Yan Wei Yangyang Zeng Yangyang Zeng Yangyang Zeng Qifan Luo Qifan Luo Qifan Luo Xuehua Sun Xuehua Sun Xuehua Sun Hui Xu Hui Xu Hui Xu Jin Peng Jin Peng Jin Peng Fuxiang Zhou Fuxiang Zhou Fuxiang Zhou |
| author_facet | Jinlin Kang Jinlin Kang Jinlin Kang Na li Na li Na li Na li Fen Wang Fen Wang Fen Wang Yan Wei Yan Wei Yan Wei Yangyang Zeng Yangyang Zeng Yangyang Zeng Qifan Luo Qifan Luo Qifan Luo Xuehua Sun Xuehua Sun Xuehua Sun Hui Xu Hui Xu Hui Xu Jin Peng Jin Peng Jin Peng Fuxiang Zhou Fuxiang Zhou Fuxiang Zhou |
| author_sort | Jinlin Kang |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T05:50:00Z |
| format | Article |
| id | doaj.art-5fd87313bd8643fdb6db6d8b127490d9 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-14T05:50:00Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-5fd87313bd8643fdb6db6d8b127490d92022-12-21T23:14:44ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-04-011310.3389/fgene.2022.832331832331Exploration of Reduced Mitochondrial Content–Associated Gene Signature and Immunocyte Infiltration in Colon Adenocarcinoma by an Integrated Bioinformatic AnalysisJinlin Kang0Jinlin Kang1Jinlin Kang2Na li3Na li4Na li5Na li6Fen Wang7Fen Wang8Fen Wang9Yan Wei10Yan Wei11Yan Wei12Yangyang Zeng13Yangyang Zeng14Yangyang Zeng15Qifan Luo16Qifan Luo17Qifan Luo18Xuehua Sun19Xuehua Sun20Xuehua Sun21Hui Xu22Hui Xu23Hui Xu24Jin Peng25Jin Peng26Jin Peng27Fuxiang Zhou28Fuxiang Zhou29Fuxiang Zhou30Department of Radiation and Medical Oncology, Zhongnan Hospital Wuhan University, Wuhan, ChinaHubei Province Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaDepartment of Radiation and Medical Oncology, Zhongnan Hospital Wuhan University, Wuhan, ChinaHubei Province Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaRenmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Radiation and Medical Oncology, Zhongnan Hospital Wuhan University, Wuhan, ChinaHubei Province Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaDepartment of Radiation and Medical Oncology, Zhongnan Hospital Wuhan University, Wuhan, ChinaHubei Province Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaDepartment of Radiation and Medical Oncology, Zhongnan Hospital Wuhan University, Wuhan, ChinaHubei Province Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaDepartment of Radiation and Medical Oncology, Zhongnan Hospital Wuhan University, Wuhan, ChinaHubei Province Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaDepartment of Radiation and Medical Oncology, Zhongnan Hospital Wuhan University, Wuhan, ChinaHubei Province Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaDepartment of Radiation and Medical Oncology, Zhongnan Hospital Wuhan University, Wuhan, ChinaHubei Province Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaDepartment of Radiation and Medical Oncology, Zhongnan Hospital Wuhan University, Wuhan, ChinaHubei Province Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaDepartment of Radiation and Medical Oncology, Zhongnan Hospital Wuhan University, Wuhan, ChinaHubei Province Key Laboratory of Tumor Biological Behaviors, Wuhan, ChinaHubei Cancer Clinical Study Center, Wuhan, ChinaPurpose: 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.https://www.frontiersin.org/articles/10.3389/fgene.2022.832331/fullmitochondiral DNAColon CancerImmunocyte infiltrationBioinformatic analysisGene signature |
| spellingShingle | Jinlin Kang Jinlin Kang Jinlin Kang Na li Na li Na li Na li Fen Wang Fen Wang Fen Wang Yan Wei Yan Wei Yan Wei Yangyang Zeng Yangyang Zeng Yangyang Zeng Qifan Luo Qifan Luo Qifan Luo Xuehua Sun Xuehua Sun Xuehua Sun Hui Xu Hui Xu Hui Xu Jin Peng Jin Peng Jin Peng Fuxiang Zhou Fuxiang Zhou Fuxiang Zhou Exploration of Reduced Mitochondrial Content–Associated Gene Signature and Immunocyte Infiltration in Colon Adenocarcinoma by an Integrated Bioinformatic Analysis Frontiers in Genetics mitochondiral DNA Colon Cancer Immunocyte infiltration Bioinformatic analysis Gene signature |
| 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 | mitochondiral DNA Colon Cancer Immunocyte infiltration Bioinformatic analysis Gene signature |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.832331/full |
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