Deciphering cervical cancer-associated biomarkers by integrated multi-omics approach

Cervical Squamous Cell Carcinoma (CESC) is one of the most fatal female malignancies, and the underlying molecular mechanisms governing this disease have not been fully explored. In this research, we planned to conduct the analysis of Gene Expression Omnibus (GEO) cervical squamous cell carcinoma microarray datasets by a detailed in silico approach and to explore some novel biomarkers of CESC.

The top commonly differentially expressed genes (DEGs) from the GSE138080 and GSE113942 datasets were analyzed by Limma package-based GEO2R tool. The protein-protein interaction (PPI) network of the DEGs was drawn through Search Tool for the Retrieval of Interacting Genes (STRING), and top 6 hub genes were obtained from Cytoscape. Expression analysis and validation of hub genes expression in CESC samples and cell lines were done using UALCAN, OncoDB, GENT2, and HPA. Additionally, cBioPortal, Gene set enrichment analysis (GSEA) tool, Kaplan-Meier (KM) plotter, ShinyGO, and DGIdb databases were also used to check some important values of hub genes in CESC.

Out of 79 DEGs, the minichromosome maintenance complex component 4 (MCM4), nucleolar and spindle-associated protein 1 (NUSAP1), cell division cycle associated 5 (CDCA5), cell division cycle 45 (CDC45), denticleless E3 ubiquitin protein ligase homolog (DTL), and chromatin licensing and DNA replication factor 1 (CDT1) genes were regarded as hub genes in CESC. Further analysis revealed that the expressions of all these hub genes were significantly elevated in CESC cell lines and samples of diverse clinical attributes. In this study, we also documented some important correlations between hub genes and some other diverse measures, including DNA methylation, genetic alterations, and Overall Survival (OS). Last, we also identify hub genes associated ceRNA network and 31 important chemotherapeutic drugs.

Through detailed in silico methodology, we identified 6 hub genes, including MCM4, NUSAP1, CDCA5, CDC45, DTL, and CDT1, which are likely to be associated with CESC development and diagnosis.