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RNA splicing and aggregate gene expression differences in lung squamous cell carcinoma between patients of West African and European ancestry.

Publication ,  Journal Article
Deveaux, AE; Allen, TA; Al Abo, M; Qin, X; Zhang, D; Patierno, BM; Gu, L; Gray, JE; Pecot, CV; Dressman, HK; McCall, SJ; Kittles, RA ...
Published in: Lung Cancer
March 2021

OBJECTIVES: Despite disparities in lung cancer incidence and mortality, the molecular landscape of lung cancer in patients of African ancestry remains underexplored, and race-related differences in RNA splicing remain unexplored. MATERIALS AND METHODS: We identified differentially spliced genes (DSGs) and differentially expressed genes (DEGs) in biobanked lung squamous cell carcinoma (LUSC) between patients of West African and European ancestry, using ancestral genotyping and Affymetrix Clariom D array. DSGs and DEGs were validated independently using the National Cancer Institute Genomic Data Commons. Associated biological processes, overlapping canonical pathways, enriched gene sets, and cancer relevance were identified using Gene Ontology Consortium, Ingenuity Pathway Analysis, Gene Set Enrichment Analysis, and CancerMine, respectively. Association with LUSC survival was conducted using The Cancer Genome Atlas. RESULTS: 4,829 DSGs and 267 DEGs were identified, including novel targets in NSCLC as well as genes identified previously to have relevance to NSCLC. RNA splicing events within 3 DSGs as well as 1 DEG were validated in the independent cohort. 853 DSGs and 29 DEGs have been implicated as potential drivers, oncogenes and/or tumor suppressor genes. Biological processes enriched among DSGs and DEGs included metabolic process, biological regulation, and multicellular organismal process and, among DSGs, ion transport. Overlapping canonical pathways among DSGs included neuronal signaling pathways and, among DEGs, cell metabolism involving biosynthesis. Gene sets enriched among DSGs included KRAS Signaling, UV Response, E2 F Targets, Glycolysis, and Coagulation. 355 RNA splicing events within DSGs and 18 DEGs show potential association with LUSC patient survival. CONCLUSION: These DSGs and DEGs, which show potential biological and clinical relevance, could have the ability to drive novel biomarker and therapeutic development to mitigate LUSC disparities.

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Published In

Lung Cancer

DOI

EISSN

1872-8332

Publication Date

March 2021

Volume

153

Start / End Page

90 / 98

Location

Ireland

Related Subject Headings

  • RNA Splicing
  • Oncology & Carcinogenesis
  • Lung Neoplasms
  • Lung
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Gene Expression
  • Carcinoma, Squamous Cell
  • 3211 Oncology and carcinogenesis
  • 3202 Clinical sciences
 

Citation

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Chicago
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Deveaux, A. E., Allen, T. A., Al Abo, M., Qin, X., Zhang, D., Patierno, B. M., … Freedman, J. A. (2021). RNA splicing and aggregate gene expression differences in lung squamous cell carcinoma between patients of West African and European ancestry. Lung Cancer, 153, 90–98. https://doi.org/10.1016/j.lungcan.2021.01.015
Deveaux, April E., Tyler A. Allen, Muthana Al Abo, Xiaodi Qin, Dadong Zhang, Brendon M. Patierno, Lin Gu, et al. “RNA splicing and aggregate gene expression differences in lung squamous cell carcinoma between patients of West African and European ancestry.Lung Cancer 153 (March 2021): 90–98. https://doi.org/10.1016/j.lungcan.2021.01.015.
Deveaux AE, Allen TA, Al Abo M, Qin X, Zhang D, Patierno BM, et al. RNA splicing and aggregate gene expression differences in lung squamous cell carcinoma between patients of West African and European ancestry. Lung Cancer. 2021 Mar;153:90–8.
Deveaux, April E., et al. “RNA splicing and aggregate gene expression differences in lung squamous cell carcinoma between patients of West African and European ancestry.Lung Cancer, vol. 153, Mar. 2021, pp. 90–98. Pubmed, doi:10.1016/j.lungcan.2021.01.015.
Deveaux AE, Allen TA, Al Abo M, Qin X, Zhang D, Patierno BM, Gu L, Gray JE, Pecot CV, Dressman HK, McCall SJ, Kittles RA, Hyslop T, Owzar K, Crawford J, Patierno SR, Clarke JM, Freedman JA. RNA splicing and aggregate gene expression differences in lung squamous cell carcinoma between patients of West African and European ancestry. Lung Cancer. 2021 Mar;153:90–98.
Journal cover image

Published In

Lung Cancer

DOI

EISSN

1872-8332

Publication Date

March 2021

Volume

153

Start / End Page

90 / 98

Location

Ireland

Related Subject Headings

  • RNA Splicing
  • Oncology & Carcinogenesis
  • Lung Neoplasms
  • Lung
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Gene Expression
  • Carcinoma, Squamous Cell
  • 3211 Oncology and carcinogenesis
  • 3202 Clinical sciences