Bioinformatics analysis of differentially expressed genes and pathways in the development of cervical cancer

Abstract

Background This study aimed to explore and identify key genes and signaling pathways that contribute to the progression of cervical cancer to improve prognosis. Methods Three gene expression profiles (GSE63514, GSE64217 and GSE138080) were screened and downloaded from the Gene Expression Omnibus database (GEO). Differentially expressed genes (DEGs) were screened using the GEO2R and Venn diagram tools. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Gene set enrichment analysis (GSEA) was performed to analyze the three gene expression profiles. Moreover, a protein–protein interaction (PPI) network of the DEGs was constructed, and functional enrichment analysis was performed. On this basis, hub genes from critical PPI subnetworks were explored with Cytoscape software. The expression of these genes in tumors was verified, and survival analysis of potential prognostic genes from critical subnetworks was conducted. Functional annotation, multiple gene comparison and dimensionality reduction in candidate genes indicated the clinical significance of potential targets. Results A total of 476 DEGs were screened: 253 upregulated genes and 223 downregulated genes. DEGs were enriched in 22 biological processes, 16 cellular components and 9 molecular functions in precancerous lesions and cervical cancer. DEGs were mainly enriched in 10 KEGG pathways. Through intersection analysis and data mining, 3 key KEGG pathways and related core genes were revealed by GSEA. Moreover, a PPI network of 476 DEGs was constructed, hub genes from 12 critical subnetworks were explored, and a total of 14 potential molecular targets were obtained. Conclusions These findings promote the understanding of the molecular mechanism of and clinically related molecular targets for cervical cancer.

Bioinformatics Screening of Potential Biomarkers from mRNA Expression Profiles to Discover Drug Targets and Agents for Cervical Cancer

“…Table 1 displayed the top five significantly enriched GO terms and KEGG pathways by involving KGs of CC diseases that are also supported by the literature review [ 17 , 19 , 23 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. The top five GO terms of the biological process, including DNA replication, cell division, G1/S transition of mitotic cell cycle, DNA replication initiation, mitotic nuclear division, were significantly enriched by the KGs sets {BRCA1, CDK1, MCM2}, {NCAPG2, AURKA, CCNB1, CDK1}, {CDK1, MCM2}, {MCM2}, and {NCAPG2, AURKA, CDK1}, respectively.…”

“…On the other hand, we reviewed 52 published articles associated with CC infections that provided transcriptome-guided hub proteins (genomic biomarkers) for cross-validation of the proposed key genes and the candidate drug agents. There were 255 hub genes reported in those 52 articles, with 7 hub proteins (AURKA, PCNA, CCNB1, CDC45, MCM2, TOP2A, CDK1) appearing in at least 5 articles ( Table S2 ) [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 23 , 24 , 25 , 26 , 27 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ]. Five (AURKA, CCNB1, MCM2, TOP2A, and CDK1) of the seven reported hub proteins were found to be similar to our suggested seven KGs.…”

“…CCNB1 played vital roles in the progression of CC through different signaling pathways [ 17 , 18 , 26 , 46 , 51 ]. CDK1 contributed to the occurrence and development of CSCC [ 18 , 23 , 25 , 26 , 27 , 40 , 41 , 44 , 46 ]. MCM2 involved in the carcinogenesis of cervical cancer [ 16 , 19 , 20 , 21 , 23 , 27 , 42 ].…”

“…CDK1 contributed to the occurrence and development of CSCC [ 18 , 23 , 25 , 26 , 27 , 40 , 41 , 44 , 46 ]. MCM2 involved in the carcinogenesis of cervical cancer [ 16 , 19 , 20 , 21 , 23 , 27 , 42 ]. TOP2A is regarded as a biomarker for the improved diagnosis of CC [ 16 , 17 , 19 , 23 , 24 , 26 , 27 , 41 , 43 , 45 ].…”

“…Transcriptomics analysis is a widely used popular approach to explore genomic biomarkers [ 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. By this time, several authors have suggested several sets of hub genes/study genes to explore molecular mechanisms and pathogenetic processes of CC [ 22 , 23 , 24 , 25 ]. CDK1 and TOP2A might play a critical role in controlling the genetic network related to cervical cancer incidence, progression, and metastasis [ 17 , 26 , 27 ].…”