Machine Learning-Based Glycolipid Metabolism Gene Signature Predicts Prognosis and Immune Landscape in Oesophageal Squamous Cell Carcinoma.

Journal: Journal of cellular and molecular medicine
PMID:

Abstract

Using machine learning approaches, we developed and validated a novel prognostic model for oesophageal squamous cell carcinoma (ESCC) based on glycolipid metabolism-related genes. Through integrated analysis of TCGA and GEO datasets, we established a robust 15-gene signature that effectively stratified patients into distinct risk groups. This signature demonstrated superior prognostic value and revealed significant associations with immune infiltration patterns. High-risk patients exhibited reduced immune cell infiltration, particularly in B cells and NK cells, alongside increased tumour purity. Single-cell RNA sequencing analysis uncovered unique cellular composition patterns and enhanced interaction intensities in the high-risk group, especially within epithelial and smooth muscle cells. Functional validation confirmed MECP2 as a promising therapeutic target, with its knockdown significantly inhibiting tumour progression both in vitro and in vivo. Drug sensitivity analysis identified specific therapeutic agents showing potential efficacy for high-risk patients. Our study provides both a practical prognostic tool and novel insights into the relationship between glycolipid metabolism and tumour immunity in ESCC, offering potential strategies for personalised treatment.

Authors

  • Lin Zhu
    Institute of Environmental Technology, College of Environmental and Resource Sciences; Zhejiang University, Hangzhou 310058, China.
  • Feng Liang
    PASTEUR, Département de Chimie, École Normale Supérieure, PSL Université, Sorbonne Université, CNRS, 75005 Paris, France.
  • Xue Han
    College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
  • Bin Ye
    Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, 2-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8573, Japan.
  • Lei Xue