Jinlin Kang1,2,3, Na Li1,2,3,4, Fen Wang1,2,3, Yan Wei1,2,3, Yangyang Zeng1,2,3, Qifan Luo1,2,3, Xuehua Sun1,2,3, Hui Xu1,2,3, Jin Peng1,2,3, Fuxiang Zhou1,2,3. 1. Department of Radiation and Medical Oncology, Zhongnan Hospital Wuhan University, Wuhan, China. 2. Hubei Province Key Laboratory of Tumor Biological Behaviors, Wuhan, China. 3. Hubei Cancer Clinical Study Center, Wuhan, China. 4. Renmin Hospital of Wuhan University, Wuhan, China.
Abstract
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.
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.
Authors: E Van Cutsem; A Cervantes; R Adam; A Sobrero; J H Van Krieken; D Aderka; E Aranda Aguilar; A Bardelli; A Benson; G Bodoky; F Ciardiello; A D'Hoore; E Diaz-Rubio; J-Y Douillard; M Ducreux; A Falcone; A Grothey; T Gruenberger; K Haustermans; V Heinemann; P Hoff; C-H Köhne; R Labianca; P Laurent-Puig; B Ma; T Maughan; K Muro; N Normanno; P Österlund; W J G Oyen; D Papamichael; G Pentheroudakis; P Pfeiffer; T J Price; C Punt; J Ricke; A Roth; R Salazar; W Scheithauer; H J Schmoll; J Tabernero; J Taïeb; S Tejpar; H Wasan; T Yoshino; A Zaanan; D Arnold Journal: Ann Oncol Date: 2016-07-05 Impact factor: 32.976