Folate metabolism-associated CYP26A1 is a clinico-immune target in colorectal cancer.

Journal: Genes and immunity
Published Date:

Abstract

Folic acid plays a crucial role in cellular regulation and metabolism, commonly included in dietary supplements. Despite this, its involvement in colorectal cancer (CRC), particularly in metabolic pathways and immune evasion, remains poorly understood. We developed the FMRG_score system using machine learning algorithms on TCGA and GEO data to assess modification patterns influencing clinical outcomes and immune characteristics in CRC. The system's reliability was validated across multiple external immunotherapy cohorts. We examined associations between FMRG-related features and clinical traits, mutation profiles, biological functions, immune infiltration, therapy responses, and drug sensitivities. By integrating in vitro and in vivo experiments with bioinformatics, we built a nine-gene risk model linked to folate metabolism for CRC prognosis. Notably, CYP26A1, a key gene in the model, was upregulated in CRC tissues, promoting cell proliferation, migration, invasion, and contributing to an immunosuppressive tumor microenvironment. Significant differences in clinical traits, immune infiltration, checkpoint expression, therapy response, and drug sensitivity were observed between risk groups. This folate-based scoring system provides a novel tool for evaluating CRC prognosis, tumor microenvironment, and response to immunotherapy. We also propose CYP26A1 as a potential oncogene in CRC, offering new therapeutic insights.

Authors

  • Yifei Zhu
    Department of Atmospheric Science, School of Environmental Sciences, China University of Geosciences, Wuhan, 430074, China.
  • Teng Zhou
    School of Computer Science and Engineering, South China University of Technology, Guangzhou 510006, China.
  • Yao Zheng
    School of Pharmaceutical Science, South-Central University for Nationalities, Wuhan, Hubei, China.
  • Yanxi Yao
    Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China.
  • Mingxi Lin
    Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China.
  • Cheng Zeng
    The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
  • Yuxin Yan
    Ningbo Huamei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang, China.
  • Yifei Zhou
    School of Mechanical Engineering, Sichuan University of Science and Engineering, Yibin, China.
  • Dou-Dou Li
    School of Clinical Medicine, Shanghai University of Medicine & Health Sciences, Shanghai, China. 17111230019@fudan.edu.cn.
  • Jian Zhang
    College of Pharmacy, Ningxia Medical University, Yinchuan, NingxiaHui Autonomous Region, China.

Keywords

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