Comparative Transcriptome Profiling Reveals Coding and Noncoding RNA Differences in NSCLC from African Americans and...

Area of Science:

• Genomics and Molecular Biology
• Oncology
• Translational Research

Background:

• Lung cancer exhibits disparities in incidence and outcomes among different racial groups.
• Understanding the molecular underpinnings of these disparities is crucial for targeted therapies.
• Previous research suggests potential genetic and microRNA (miRNA) expression differences between African Americans (AAs) and European Americans (EAs).

Purpose of the Study:

• To investigate racial differences in gene and miRNA expression in lung tumors between AAs and EAs.
• To determine if these molecular differences correlate with distinct lung tumor biology and clinical relevance.
• To assess the implications for drug response and immunotherapy in different populations.

Main Methods:

• Comparative molecular profiling of mRNA and miRNA expression in normal and tumor tissues from AAs and EAs.
• Utilized data from the NCI-Maryland Case Control Study including patients undergoing curative NSCLC surgery.
• Assessed pathway enrichment, predicted drug response, tumor microenvironment infiltration, and immunotherapy antigen profiling.

Main Results:

• AA-enriched differential gene expression was linked to stem cell and invasion pathways, while EA-enriched expression involved cell proliferation pathways.
• Population-specific gene expression was partly driven by distinct miRNA expression profiles.
• Drug susceptibility predictions showed inverse correlations: AA resistance and EA sensitivity. Significant differences in M1/M2 macrophage infiltration were observed in AAs, but PD-L1/PD-L2 expression was similar.

Conclusions:

• Comparative transcriptomic profiling reveals significant differences in lung tumor biology between AAs and EAs.
• These molecular disparities may explain differential responses to therapies.
• Increased participation of AAs in lung cancer clinical trials is essential to leverage these transcriptomic differences for improved therapeutic benefits in all populations.