IDENTIFICATION OF HUB GENES AND miRNA ASSOCIATED WITH MERKEL CELL CARCINOMA BY INTEGRATED BIOINFORMATICS ANALYSIS

Abstract

Merkel Cell Carcinoma is a highly aggressive form of non-melanoma skin cancer. Due to the rarity of the disease, MCC remains a cancer type that is yet to be fully researched. This is of immediate significance now as the incidences of MCC have been on a rise and the disease is often associated with fatality. Therefore, the purpose of this study was to explore the presence of crucial genes and miRNAs involved in Merkel Cell Carcinoma based on microarray analysis. The expression profile data of GSE39612 and GSE45146 were obtained from Gene Expression Omnibus. The differentially expressed genes (DEGs) were screened, followed by functional enrichment analysis, protein-protein interaction (PPI) network construction and analysis of significant network modules. Hub genes were identified using MCODE and cytoHubba plug-in. After the DE miRNAs were screened, their putative target genes were identified by TargetScan, miRDB and miRTarBase. The overlapped genes found between the putative targets and the DEGs were used to construct a DEG-DEmiR network in Cytoscape. Lastly, hub miRNAs present in the DEGsDEmiR network were identified and annotated. A total of 449 DEGs were identified including 164 upregulated genes and 285 downregulated genes. DEGs were mostly enriched in epidermis development, keratinocyte differentiation, structural molecule activity, cAMP signalling pathway, calcium signalling pathway and oocyte meiosis. Using the results of MCODE and cytoHubba, 3 significant clusters were extracted from the PPI network and 16 genes (AURKA, FLG, KIF4A, DSG1, PKP1, LOR, BUB1, CDC6, CENPE, CXCR4, FOXM1, CXCL12, CDSN, DSG3, IVL and DSP) were selected as core protein-coding DEGs based upon their topological parameters. Besides, a total of 17 DEmiRs were identified, including 16 downregulated and 1 upregulated miRNA. 56 pairs of validated DEGs-DEmiRs and 221 pairs of predicted DEGs-DEmiRs were curated from miRTarBase and TargetScan & miRDB respectively. Finally, Network Analyser was used to identify the following as hub miRNA: hsa-miR-1, hsa-miR-19a, hsa-miR-9-5p, hsa-miR-9-3p, hsa-miR-454 and hsa-miR-195-3p.