ORIGINAL RESEARCH article
Front. Med.
Sec. Gastroenterology
Volume 12 - 2025 | doi: 10.3389/fmed.2025.1618471
This article is part of the Research TopicResearch on Biomarkers for Immunotherapy in Gastrointestinal Tumors: Basic Exploration and Clinical ApplicationView all articles
Constructing a novel mitochondrial metabolism-related genes signature to evaluate tumor immune microenvironment and predict survival of colorectal cancer
Provisionally accepted
- 1Department of Endocrine and Metabolic Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- 2China National Research Center for Metabolic Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- 3Key Laboratory of Shanghai Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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AbstractBackground: Colorectal cancer (CRC) is a highly lethal gastrointestinal malignancy with substantial global health implications. Although mitochondrial metabolism genes play a crucial role in CRC development, their prognostic significance remains unclear.Methods: This study systematically analyzed the expression and prognostic value of mitochondrial metabolism-related genes in CRC patients, establishing a risk model using data from TCGA and GEO databases. We also investigated the tumor microenvironment (TME), immune cell infiltration, tumor mutation burden, microsatellite instability (MSI), and drug sensitivity. Core mitochondrial metabolism-related gene, TMEM86B was identified and its functions validated through cell-based assays and in vivo mouse models.Results: Fifteen mitochondrial metabolism-related genes were identified, including HSD3B7, ORC1, GPSM2, NDUFA4L2, CHDH, LARS2, TMEM86B, FABP4, TNFAIP8L3, HMGCL, GDE1, ACOX1, ARV1, HDC, and GSR. The nomogram, which incorporates independent prognostic genes TMEM86B, TNFAIP8L3, HDC, and key clinical features pTNM stage (pathological Tumor-Node-Metastasis), age, was created to predict patient outcomes. Notable differences in immune cell infiltration were observed between risk groups. The risk score was associated with TME genes and immune checkpoints, indicating an immunosuppressive environment in high-risk groups. Furthermore, TIDE analysis revealed that integrating the risk score with immune score, stromal score, or microsatellite status improved the prediction of immunotherapy response across different CRC patient subgroups. Core mitochondrial metabolism-related gene, TMEM86B promotes colorectal cancer progression by enhancing cell proliferation, migration, and invasion, and its downregulation significantly inhibits tumor growth both in vitro and in vivo.Conclusions: Our findings indicate that the risk model associated with mitochondrial metabolism may serve as a dependable prognostic indicator, facilitating tailored therapeutic strategies for CRC patients. TMEM86B promotes colorectal cancer progression, and its downregulation inhibits tumor growth in vitro and in vivo.Keywords: Colorectal cancer, Prognostic biomarker, Mitochondrial metabolism, Tumor microenvironment, Immunotherapy, Drug susceptibility
Keywords: colorectal cancer, prognostic biomarker, mitochondrial metabolism, Tumor Microenvironment, Immunotherapy, Drug Susceptibility
Received: 26 Apr 2025; Accepted: 24 Jun 2025.
Copyright: © 2025 Wang, Zhang and Ning. 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: Hou Wang, Department of Endocrine and Metabolic Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China
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