| Abstrakt: |
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 and five-year survival rate of less than 5% of patients necessitates this research which identifies targetable genes to understand resistive mechanisms and mitigate poor prognosis. Public single-cell RNA sequencing (scRNA-Seq) 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 associated with resistive mechanisms and prominent genes found in the leading edge subset of GSEA were visualized in RStudio and analyzed in Gene Expression Profiling Interactive Analysis 2 (GEPIA2) for survival impact. In this unsupervised study, the reactive oxygen species (ROS) and TGF-beta signaling pathways were two upregulated gene sets shared by both treatment types, supporting their association with resistive SCLC. Identified, shared leading edge subset genes of the ROS pathway included TXN, TXNRD1, NDUFB4, and LAMTOR5, which have been noted to 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 have associated with the promotion of epithelial mesenchymal transitions, suppression of immune response, and increased tumor growth. This study identifies novel genes, previously unassociated with SCLC, that play a role in treatment refraction development in SCLC. Further experimentation may validate their potential as therapeutic targets to resensitize tumors and improve prognosis for individuals with resistant SCLC. [ABSTRACT FROM AUTHOR] |
