AUTHOR=Wang Hou 

TITLE=A mitochondrial ferroptosis-related gene signature predicts prognosis and immune landscape in colon cancer

JOURNAL=Frontiers in Medicine

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1614012

DOI=10.3389/fmed.2025.1614012

ISSN=2296-858X

ABSTRACT=BackgroundColon cancer is a highly aggressive gastrointestinal malignancy with significant global health implications. Although mitochondrial ferroptosis-related genes have been implicated in colon cancer progression, their prognostic significance remains inadequately understood.MethodsWe conducted a comprehensive analysis of the expression patterns and prognostic value of mitochondrial ferroptosis-related genes in patients with colon cancer, utilizing data from the TCGA and GEO databases. A prognostic risk model was established, followed by evaluations of the tumor microenvironment (TME), immune cell infiltration, tumor mutation burden (TMB), and predicted drug sensitivity. P4HA1, recognized as an important mitochondrial ferroptosis-associated gene, was selected for functional characterization using in vitro experiments.ResultsFour key mitochondrial ferroptosis-associated genes—PDSS2, GRSF1, SLC39A8, and P4HA1—were identified. A nomogram combining the risk score and pTNM stage was constructed to predict patient outcomes. Immune microenvironment analysis revealed distinct differences in immune cell infiltration between the high- and low-risk groups. The risk score was significantly correlated with the expression of TME-related genes and immune checkpoint molecules, suggesting a more immunosuppressive microenvironment in high-risk patients. Furthermore, integrating the risk score with TMB enhanced the accuracy of survival prediction. Silencing P4HA1 markedly reduces the proliferative and migratory abilities of colorectal cancer cells in vitro.ConclusionThis mitochondrial ferroptosis-based risk model represents a promising prognostic biomarker and may offer valuable insights for personalized treatment strategies in colon cancer management. P4HA1 facilitates the advancement of colorectal cancer, while its suppression diminishes the in vitro proliferation and migration of colorectal cancer cells.