Bioinformatics Analysis of Key Genes and miRNAs Associated with Small-cell Lung Cancer

Abstract

Small-cell lung cancer (SCLC) is a type of lung cancer, accounting for approximately 15% of lung cancers. SCLC is significantly associated with early recurrence, metastasis, and poor prognosis, with a 2-year survival rate after therapy, which is <5%. The molecular mechanisms underlying the development of SCLC are not clear. In this study, we identified SCLC-specific biomarkers by evaluating the differential expression of mRNA and microRNA (miRNA) profiles in SCLC tissue compared with normal lung tissue. A non-coding RNA sequence dataset (GSE19945) and transcriptome sequencing dataset (GSE6044) were downloaded from the GEO database. We identified 445 DEGs (differentially expressed genes) and 128 DE-miRNAs (differentially expressed miRNAs) using the GEO2R tool of the GEO and R limma software package. Furthermore, using the KEGG database, we identified 15 enrichment pathways, mostly associated with DNA replication, cell cycle, and oocyte meiosis mismatch repair, and the GO function was considerably enriched for 26 items. To investigate the molecular processes of key signaling pathways and cellular activity in SCLC, we used Cytoscape software to construct protein-protein interaction (PPI) networks. Using miRNAWalk, we identified 598 target genes of the 1380 miRNAs and constructed miRNA target networks. In addition, we identified eighteen overlapping genes that are regulated by 28 different miRNAs. The identified hub genes are important because they may be used as biomarkers for prognosis, diagnosis, and therapeutic target for SCLC.