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RNA Sequencing To Characterize Pathways in EGFR-Mutated Non-Small Cell Lung Cancer

ASCO 2023 Abstract
Authors Nicole Yun, Ankur D Naqib, Jeffrey Allen Borgia, Marta Batus, Mary Jo J. Fidler

Background:The purpose of our study is to explore patterns in gene expression for patients with EGFR-mutated non-small cell lung cancer (NSCLC).

Methods:287 patients with EGFR-mutated lung cancer were identified using the Tempus Lens database. Raw RNA sequence expression data was requested from TEMPUS XT RNA analysis. Sequences were processed through the EdgeR analysis in the R programming environment. Differential abundance analysis was done to further filter out genes and Benjamini-Hochberg correction selected genes with a corrected p-value of < 0.05 for further pathway analysis. Pathway analysis was performed using GSEA (Gene Set Enrichment Analysis). Enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and GSEA Molecular Signatures Database (MsigDB) was performed for overexpressed and under-expressed genes in patients.

Results:Pathway analysis run against the KEGG reference database and GSEA MSigDB helped to illustrate genes shared in activated and suppressed pathways in our patient cohort. For example, using the KEGG reference database, enriched pathways meeting p value significance threshold of < 0.005 included the nicotine addiction, olfactory transduction, and cortisol synthesis and secretion pathways, amongst others. Suppressed pathways using the KEGG reference database meeting p value significance threshold of < 0.005 included fat digestion and absorption, vitamin digestion and absorption, PPAR signaling pathway, and drug metabolism by cytochrome P450 and other enzymes. Using the GSEA MSigDB, enriched pathways included G protein-coupled receptor activity, sensory perception, synaptic signaling and trans-synaptic signaling, meanwhile suppressed pathways included cytolysis by host of symbiont cells, negative regulation of very-low-density lipoprotein particle remodeling, and oxidoreductase activity.

Conclusions:Patterns in gene and pathway expression were observed in our cohort of patients with EGFR-mutated NSCLC. Analyzing RNA sequencing pathways showed differential up and down regulation of multiple pathways. For example, suppression of the fat and vitamin digestion and absorption pathways may shed light on processes involved in cancer cachexia and metabolism. Though further work needs to be done, RNA sequencing results for patients with EGFR-mutated lung cancer may lead to information on cancer development and additional therapeutic targets.