SPARC related signaling genes in non-small cell lung cancer by RNA-sequencing transcriptome analysis

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for about 80 % cases of lung cancer and is the leading cause of cancer-related death in the United States and worldwide. SPARC (secreted protein acidic and rich in cysteine), a multicellular non-structural glycoprotein is known to be involved in the regulation of cell adhesion, cell proliferation as well as in tumorigenesis and metastasis in various cancers including NSCLC. SPARC contributes to matrix remodeling and turnover and is involved in modulating the tumor microenvironment. Previous studies have suggested that SPARC can be used as a prognostic factor for NSCLC and represents a highly promising therapeutic modality. In this study we used high-throughput RNA-sequencing transcriptome profiling analysis to delineate pathways involved in SPARC signaling. We assessed differentially expressed genes, novel genes, biological processes and biological signaling pathways in SPARC expressed NSCLC cell line. We identified a total of 3,280 upregulated and 1,608 downregulated differentially expressed genes with known functions in SPARC expressed NSCLC cells. KEGG enrichment analysis indicated that the differentially expressed genes were involved in cellular metabolic processes, regulation of biological processes or biological signaling pathways like cell cycle, spliceosome, apoptosis and WNT signaling pathway. The RNA-seq analysis further revealed that genes involved in apoptosis were significantly altered after SPARC modulation to NSCLC cells. Co-transfection experiments using SPARC shRNA indicated that SPARC modulation induced apoptosis via regulating PI3K/AKT signaling pathway. In summary, this study uncovers SPARC dependent regulatory mechanisms in NSCLC. Note: This abstract was not presented at the meeting. Citation Format: Sajani S. Lakka, Bhavesh K. Ahir. SPARC related signaling genes in non-small cell lung cancer by RNA-sequencing transcriptome analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3518.