A novel signature model based on mitochondrial-related genes for predicting survival of colon adenocarcinoma

Abstract

Background: Colon cancer is the foremost reason of cancer-related mortality worldwide. Colon adenocarcinoma constitutes 90% of colon cancer, and most patients with colon adenocarcinoma (COAD) are identified until advanced stage. With the emergence of an increasing number of novel pathogenic mechanisms and treatments, the role of mitochondria in the development of cancer, has been studied and reported with increasing frequency.

Methods: We systematically analyzed the effect of mitochondria-related genes in COAD utilizing RNA sequencing dataset from The Cancer Genome Atlas database and 1613 mitochondrial function-related genes from MitoMiner database. Our approach consisted of differentially expressed gene, gene set enrichment analysis, gene ontology terminology, Kyoto Encyclopedia of Genes and Genomes, independent prognostic analysis, univariate and multivariate analysis, Kaplan-Meier survival analysis, immune microenvironment correlation analysis, and Cox regression analysis.

Results: Consequently, 8 genes were identified to construct 8 mitochondrial-related gene model by applying Cox regression analysis, CDC25C, KCNJ11, NOL3, P4HA1, QSOX2, Trap1, DNAJC28, and ATCAY. Meanwhile, we assessed the connection between this model and clinical parameters or immune microenvironment. Risk score was an independent predictor for COAD patients' survival with an AUC of 0.687, 0.752 and 0.762 at 1-, 3- and 5-year in nomogram, respectively. The group with the highest risk score had the lowest survival rate and the worst clinical stages. Additionally, its predictive capacity was validated in GSE39582 cohort.

Conclusion: In summary, we established a prognostic pattern of mitochondrial-related genes, which can predict overall survival in COAD, which may enable a more optimized approach for the clinical treatment and scientific study of COAD. This gene signature model has the potential to improve prognosis and treatment for COAD patients in the future, and to be widely implemented in clinical settings. The utilization of this mitochondrial-related gene signature model may be benefit in the treatments and medical decision-making of COAD.

Keywords: Colon adenocarcinoma (COAD); Immune checkpoint; Mitochondrial-related genes; Overall survival (OS); Risk score; Signature.