Gene expression-based modeling of overall survival in Black or African American patients with lung adenocarcinoma

Front Immunol. 2024 Nov 11:15:1478491. doi: 10.3389/fimmu.2024.1478491. eCollection 2024.

Abstract

Introduction: Lung cancer is a leading cause of cancer-related deaths worldwide. Black/African American (B/AA) populations, in particular, exhibit the highest incidence and mortality rates of lung adenocarcinoma (LUAD) in the United States.

Methods: This study aims to explore gene expression patterns linked to LUAD in B/AA and case-matched white patients, with the goal of developing predictive models for prognosis. Leveraging RNA sequencing data from The Cancer Genome Atlas (TCGA) database, genes and pathways associated with overall survival (OS) were identified.

Results: The OS-associated genes in B/AA patients were distinct from those in white patients, showing predominant enrichment in immune-related pathways. Furthermore, mRNA co-expression network analysis revealed that OS-associated genes in B/AA patients had higher levels of interaction with various pathways, including those related to immunity, cell-ECM interaction, and specific intracellular signaling pathways. Notably, a potential B/AA-specific biomarker, C9orf64, demonstrated significant correlations with genes involved in immune response. Unsupervised machine learning algorithms stratified B/AA patients into groups with distinct survival outcomes, while supervised algorithms demonstrated a higher accuracy in predicting survival for B/AA LUAD patients compared to white patients.

Discussion: In total, this study explored OS-associated genes and pathways specific for B/AA LUAD patients. Further validation and clinical application of these findings are warranted to address disparities and improve outcomes in diverse patient populations.

Keywords: African American; expression network; immune response; lung adenocarcinoma; machine learning; overall survival; race disparity.

MeSH terms

  • Adenocarcinoma of Lung* / genetics
  • Adenocarcinoma of Lung* / immunology
  • Adenocarcinoma of Lung* / mortality
  • Aged
  • Biomarkers, Tumor / genetics
  • Black or African American* / genetics
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / immunology
  • Lung Neoplasms* / mortality
  • Male
  • Middle Aged
  • Prognosis
  • Transcriptome
  • White

Substances

  • Biomarkers, Tumor

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was funded by grant P20CA252717 (RW) from the National Institutes of Health.