Heliyon (Nov 2024)
Novel bioinformatic approaches show the role of driver genes in the progression of cervical cancer: An in-silico study
Abstract
Background: The goal of this bioinformatics research is to get a comprehensive understanding of the driver genes and their function in the development, progression, and treatment of cervical cancer. This study constitutes a pioneering attempt, adding to our knowledge of genetic diversity and its ramifications. Material and methods: In this project, we use bioinformatics and systems biology methods to identify candidate transcription factors and the genes they regulate in order to identify microRNAs and LncRNAs that regulate these transcription factors and lead to the discovery of new medicines for the treatment of cervical cancer. From the differentially expressed genes available via GEO's GSE63514 accession, we use driver genes to choose these candidates. We then used the WGCNA tool in R to rebuild the co-expression network and its modules. The hub genes of each module were determined using CytoHubba, a Cystoscope plugin. The biomarker potential of hub genes was analyzed using the UCSC Xena browser and the GraphPad prism program. The TRRUST database is used to locate the TFs that regulate the expression of these genes. In order to learn how drugs, MicroRNAs, and LncRNAs interact with transcription factors, we consulted the Drug Target Information Database (DGIDB), the miRWalk database, and the LncHub database. Finally, the online database Enrichr is utilized to analyze the enrichment of Gene Ontology and KEGG pathways. Results: By combining the mRNA expression levels of 2041 driver genes from 14 early-stage Cervical cancer and 24 control samples, a co-expression network was built. The cluster analysis shows that the collection of shared genes may be broken down into seven distinct groups, or ''modules.'' According to the average linkage hierarchical clustering and Summary smaller than 2, we found five modules (represented by the colors blue, brown, red, green, and grey) in our research. Then, we identify 5 high-degree genes from these modules that may serve as diagnostic biomarkers (ZBBX, PLCH1, TTC7B, DNAH7, and ZMYND10). In addition, we identify four transcription factors (SRF, RELA, NFKB1, and SP1) that regulate the expression of genes in the co-expression module. Drugs, microRNAs, and long noncoding RNAs are then shown to cooperate with transcription factors. At last, the KEGG database's pathways were mined for information on how the co-expression module fits within them. More clinical trials are required for more trustworthy outcomes, and we collected this data using bioinformatics methods. Conclusion: The major goal of this research was to identify diagnostic and therapeutic targets for cervical cancer by learning more about the involvement of driver genes in cancer's earliest stages.