ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
This article is part of the Research TopicInnovative Strategies for the Discovery of New Therapeutic Targets in Cancer TreatmentView all 15 articles
Novel mtDNA methylation-associated prognostic signatures in colorectal cancer
Provisionally accepted
- Department of Colorectal Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Given the high morbidity and mortality of colorectal cancer (CRC), as well as its challenging treatment, the present study was conducted to identify reliable prognostic signatures for predicting clinical outcomes. Methods: This study identified key genes through differential expression analysis and cluster analysis on CRC transcriptomic data from public databases and mitochondrial DNA methylation-related genes (MDM-RGs) from previous literature. Cox analysis and machine learning were used to define prognostic genes and build a prognostic model, followed by the establishment of a nomogram to assess the risk score as a prognostic indicator. Furthermore, the impact of prognostic genes was explored by employing immune infiltration, anti-tumor immunoassay, medication sensitization assay, and prognostic gene dependency analysis. In addition, the expression of MDM-RGs in CRC was assessed by qPCR and western blotting. Results: Consequently, this study identified three prognostic MDM-RGs (TINAG, EPHB2, and FCN3), and a risk model was constructed based on these three prognostic genes. A nomogram was created to predict CRC prognosis clinically. Significant differences in risk scores were observed across subgroups, particularly in Stage and T stage groups. This study observed disparities in immune cells involving lymphocytes and memory cells, with the identification of 92 pharmaceuticals showing inter-group significant differences. Sorafenib, Salubrinal, and Roscovitine were positively correlated with the risk score, while WO2009093972 was negatively correlated. Additionally, this study identified several target genes such as FBXO25 with TINAG, CCDC28A with EPHB2, and SH2D6 with FCN3, with subsequent validation achieved through qPCR and western blotting. Conclusions: In conclusion, this study identifies three prognostic genes, providing new insights into CRC pathogenesis and potential therapeutic strategies.
Keywords: colorectal cancer, drug sensitivity, Immune infiltration, Mitochondrial DNA methylation, Prognostic genes
Received: 13 Aug 2025; Accepted: 03 Dec 2025.
Copyright: © 2025 Wang, Chen, Li, Zhang, Li and Zhan. 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) or licensor 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.
* Correspondence:
Qiang Wang
Wei Zhan
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.