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Abstract: Treatment refraction is a hallmark of small cell lung cancer (SCLC), occurring in almost 80% of patients after initial response to current treatment modalities. The aggressive nature of this cancer and 5-year survival rate of less than 5% in patients necessitates further research to understand resistive mechanisms, identify biomarkers, and mitigate poor prognosis. Single cell RNA sequencing datasets of untreated and DNA damage repair inhibitor (DDRi) treated samples were obtained through the Gene Expression Omnibus. Gene set enrichment analysis (GSEA) was performed to identify upregulated pathways, elucidating resistive mechanisms present in treated, relapsed samples. Prominent genes in the leading edge subset of GSEA were visualized in RStudio and analyzed in GEPIA2 for their impact on survival. Reactive oxygen species (ROS) pathway and TGF Beta Signaling pathway were two upregulated gene sets shared by both treatment types. Shared leading edge subset genes of the ROS pathway included TXN, TXNRD1, NDUFB4, and LAMTOR5, which allow cancerous cells to evade apoptosis and promote cell proliferation. Shared leading edge subset genes of the TGF Beta Signaling pathway included HDAC1, CTNNB1, and SLC20A1, which promote epithelial mesenchymal transitions, suppressed immune response, and increased tumor growth. This study identifies novel genes that play a role in the development of treatment refraction in SCLC, and further experimentation may validate their potential as therapeutic targets to resensitize tumors.
KEYWORDS: lung cancer, small cell lung cancer, oncology, bioinformatics, genomics
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