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Global profiling of alternative splicing in non-small cell lung cancer reveals novel histological and population differences

  • 0Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, USA.
Oncogene +

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January 9, 2025

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January 9, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

African-American men face higher lung cancer risks. This study identifies novel alternative splicing biomarkers in lung tumors, offering insights into population-specific differences and potential new therapies to advance health equity.

Area Of Science

  • Genomics
  • Oncology
  • Molecular Biology

Background

  • Lung cancer disproportionately affects African-American (AA) men compared to European-American (EA) men, with higher incidence and mortality rates.
  • Understanding molecular differences in lung cancer between populations is crucial for targeted therapies and health equity.

Purpose Of The Study

  • To identify high-confidence alternative splicing (AS) events in lung tumors from AA and EA men.
  • To discover novel AS biomarkers associated with oncogenic pathways and population-specific differences in lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC).

Main Methods

  • High-throughput, high-depth total RNA sequencing of lung tumors and adjacent non-tumor tissues (NATs) from two independent cohorts.
  • Analysis of differential percent spliced in (PSI) values to identify significant AS events.
  • Validation of cancer signatures using high-throughput reverse transcription-PCR.

Main Results

  • Identified novel AS biomarkers with differential PSI values between tumors and NATs, enriched in AA and EA populations.
  • Uncovered tumor subtype- and population-specific AS events linked to cell surface proteins and cancer driver genes.
  • Highlighted significant AS events in SYNE2 (LUAD, both populations), CD44 (LUAD, EAs), and TMBIM6 (LUAD, AAs).

Conclusions

  • This comprehensive survey of lung tumors provides a valuable resource for understanding molecular subtypes between AA and EA populations.
  • The identified AS events and biomarkers may reveal new therapeutic vulnerabilities, potentially advancing health equity in lung cancer treatment.

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