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.

The anoikis-related gene signature predicts survival accurately in colon adenocarcinoma

“…Cui Tang’ research results showed that HOXB13 plays a tumor-promoting role in HCC cells, promotes HCC drug resistance by up-regulating CDC25C, and improves the ability of cells to resist anoikis 45 . These studies found that CDC25C may be an important target gene in patients with COAD because they are related to metabolism, cell cycle and tumor progression 46 , 47 . Mariana Toricelli found that Timp1 confers cell survival through activation of the PDK1 pathway and that Timp1 and AKT cooperate to confer resistance to anoikis in metastatic melanoma cells 48 .…”

A Comprehensive Prognostic Model for Colon Adenocarcinoma Depending on Nuclear-Mitochondrial-Related Genes

“… 16 Gao et al has made the first attempt to identify multi-gene markers of mitochondria-related genes and evaluate their potential function in COAD. 17 However, we constructed the prognostic model for COAD containing these nine genes at the first time. Our results, which showed OS has a greater AUC value at 1, 3 and 5 years, seem to have better prognostic efficacy.…”

“…Studies on the role of mitochondria-associated genes in predicting COAD prognosis are still insufficient. 17 Alterations in mitochondrial metabolic pathways may impact colon cancer cell proliferation and invasion. 43 We focused on researching mitochondria-associated genes and innovatively discovered nine biomarkers.…”

“…Some studies have been carried out to investigate the function of mitochondria-related genes in COAD. 16 , 17 Nevertheless, studies on the function and efficacy of mitochondria-related genes in prognosticating COAD have been inadequate and the relationship between mitochondrial genes and COAD still remains largely unknown. 18 Therefore, the study aims to employ bioinformatics and molecular biology techniques for the identification of mitochondrial biomarkers associated with COAD.…”

Downregulation of HIGD1B induces mitochondria‐mediated apoptosis in gastric cancer cells by inactivating Akt and ERK pathways

“…Enhanced mitochondrial dysfunction can inhibit cancer cell proliferation and metastasis (Jiaqi et al, 2023). Moreover, there is growing evidence indicating that some mitochondria‐related genes (e.g., AREG and CCND1) can predict the prognosis of cancer patients (Gao & Xing, 2022; Li et al, 2023).…”