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Pan-cancer analyses reveal cancer-type-specific autophagy signatures with potential implications for prognosis and

Hongyan Yuan1, Xiaojing Zhu1, Jiaxing Zhang1

  • 1College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.

Journal of Cancer
|January 2, 2025
PubMed

Insights

Autophagy-related genes (ATGs) show differential expression across 21 cancers. An autophagy-related score (ATS) predicts prognosis and therapy response, highlighting autophagy's value in cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Autophagy is a vital cellular process implicated in cancer development, progression, and immune regulation.
  • A comprehensive understanding of autophagy-related genes (ATGs) across diverse cancer types is currently lacking.
  • Systematic pan-cancer analysis is needed to explore the prognostic and therapeutic implications of autophagy.

Purpose of the Study:

  • To conduct a transcriptome-based pan-cancer analysis of autophagy.
  • To assess the prognostic and therapeutic response predictive value of autophagy-related genes (ATGs).
  • To investigate the influence of autophagy on the tumor immune microenvironment.

Main Methods:

  • Performed a transcriptome-based pan-cancer analysis of autophagy-related genes (ATGs).
  • Developed and validated an autophagy-related score (ATS) based on differentially expressed ATGs.
  • Utilized single-cell analysis to examine T cell and macrophage interactions in bladder urothelial carcinoma (BLCA).
  • Correlated ATS with drug sensitivity and predicted therapy response.

Main Results:

  • Found differential expression of 3-32% of ATGs across 21 human cancers.
  • The developed ATS accurately predicted prognosis in 11 cancer types, validated across independent datasets.
  • Autophagy influences the tumor immune microenvironment by regulating tumor-infiltrating lymphocytes and myeloid-derived cells.
  • Lower ATS correlated with enhanced T cell and macrophage interactions, improving clinical outcomes in BLCA.
  • ATS demonstrated a correlation with drug sensitivity and predictive capacity for therapy response.

Conclusions:

  • Autophagy-related genes (ATGs) exhibit significant differential expression across various human cancers.
  • The autophagy-related score (ATS) serves as a robust biomarker for predicting cancer prognosis and therapy response.
  • Autophagy plays a critical role in shaping the tumor immune microenvironment and influences treatment efficacy.
  • These findings underscore the substantial clinical value of targeting autophagy in cancer treatment strategies.
Keywords:
AutophagyCancerPrognosisTherapy responseTumor microenvironment

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