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Machine Learning Identifies Pan-Cancer Landscape of Nrf2 Oxidative Stress Response Pathway-Related Genes

Na Li1,2, Xianquan Zhan1,2,3

  • 1Shandong Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, 440 Jiyan Road, Jinan, Shandong 250117, China.

Oxidative Medicine and Cellular Longevity
|March 4, 2022
PubMed
Abstract

Insights

This study reveals how Nrf2 pathway genes impact cancer by linking their expression to tumor characteristics and patient outcomes. Prognostic models using these genes show significant associations with survival across various cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Oxidative stress and reactive oxygen species (ROS) influence cell fate and are regulated by the Nrf2 signaling pathway.
  • The Nrf2 pathway controls the expression of genes involved in apoptosis, antioxidant defense, detoxification, and drug transport.

Purpose of the Study:

  • To conduct a systematic pan-cancer analysis of Nrf2 signaling pathway-related genes.
  • To investigate the relationship between Nrf2 pathway gene expression and various cancer hallmarks, including tumor mutation burden, immune characteristics, and drug sensitivity.
  • To develop prognostic models for specific cancers based on Nrf2 pathway genes.

Main Methods:

  • Selected Nrf2-related genes for systematic pan-cancer analysis across 11,057 subjects from 33 cancer types.
  • Utilized Spearman correlation analysis to assess relationships between gene expression and tumor mutation burden, microsatellite status, clinical features, immunity, stemness, and drug sensitivity.
  • Constructed prognosis models using Cox regression and least absolute shrinkage and selection operator (Lasso) regression for lung squamous carcinoma, breast cancer, and stomach cancer.

Main Results:

  • Identified differential expression of many Nrf2 pathway genes between tumor and normal tissues, with PIK3CA showing a high mutation rate.
  • Demonstrated significant correlations between Nrf2 pathway gene expression and tumor mutation burden, copy number variants, microsatellite instability, survival, pathological stage, immune parameters, cancer stemness, and drug sensitivity.
  • Validated prognostic models in lung squamous carcinoma, breast cancer, and stomach cancer, showing significant associations with survival rates and clinicopathological characteristics.

Conclusions:

  • Provided a comprehensive pan-cancer landscape of Nrf2 pathway-related genes.
  • Developed distinct prognostic models for different cancer types based on shared Nrf2 pathway genes, highlighting their clinical relevance.

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