Integrative methylation and transcriptomic analysis reveals key genes linking cellular senescence and metabolic

Xiaochen Ma1, Lu Chen2, Chenhe Yi1

  • 1Department of General Surgery, Hepatobiliary Surgery Center, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai, China.

Bioscience Trends
|November 3, 2025
PubMed

Insights

This study uncovers a five-gene signature linking epigenomic changes to cellular senescence and metabolic reprogramming in colorectal liver metastasis (CRLM). This molecular hub may serve as a biomarker for patient stratification and targeted therapies.

Area of Science:

  • Oncology
  • Genomics
  • Epigenetics

Background:

  • Colorectal liver metastasis (CRLM) is a significant cause of cancer mortality.
  • The interplay between cellular senescence, metabolic reprogramming, and epigenomic alterations in CRLM is not well understood.

Purpose of the Study:

  • To identify key genes and pathways involved in the epigenomic rewiring of CRLM.
  • To discover a molecular signature for potential use in patient stratification and therapeutic strategies.

Main Methods:

  • Integrated genome-wide DNA methylation and RNA-seq data from paired primary tumors and liver metastases.
  • Applied machine learning (LASSO + SVM-RFE) to identify a gene signature.
  • Performed gene-set enrichment and immune deconvolution analyses.

Main Results:

  • Identified a five-gene signature (CXCL1, SERPINE1, NDRG1, SRM, GATM) associated with CRLM, characterized by hypomethylation and overexpression.
  • These genes are implicated in pathways like oxidative phosphorylation and focal adhesion.
  • Signature genes correlated with immunosuppressive immune cells and modulated chemo-resistance.

Conclusions:

  • A five-gene epigenetic-transcriptomic signature is identified in colorectal liver metastasis.
  • This signature holds potential as a biomarker for patient stratification and combination therapy development.

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