Discovery of novel six genes-based cervical cancer-associated biomarkers that are capable to break the heterogeneity barrier and applicable at the global level
Yasir Hameed, Mehran Khan
Abstract
Background: Although previous studies have identified the cervical cancer biomarkers by utilizing gene expression omnibus (GEO) expression datasets, they are limited in their application because of the heterogeneity-specific natures. Therefore, the present study was initiated to discover the GEO-based cervical cancer biomarkers that could employ over the heterogeneity barrier. Methods: Initially, the already reported cervical cancer-associated hub genes were mined and extracted through the literature search. Then, a protein-protein interaction network was developed and analyzed to discover six more closely cervical cancer-linked hub genes (real hub genes). Later, a comprehensive bioinformatics approach was applied to determine the diagnostic and prognostic potential of the real hub genes in cervical cancer patients of different clinicopathological features. Results: From a pool of 110 collected hub genes, in total 6 genes (CDK1, CCNB1, topoisomerase 2 alpha, checkpoint kinase 1, AURKA, and CDC6) were regarded as the real hub genes. Expression analysis revealed the significant upregulation of the real hub genes in cervical cancer patients of different races, cancer stages, body weights, and age groups. Further, correlational analyses have shown different interesting correlations between the expression and various other parameters of the real hub genes including promoter methylation status, genetic alteration, overall survival duration, tumor purity, and CD8+ T immune cells infiltration. Finally, related to hub genes, we have also identified potential miRNAs and chemotherapeutic drugs showing a great therapeutic potential. Conclusion: We have discovered a set of six real hub genes that might be utilized as new biomarkers for cervical cancer patients of different clinicopathological characteristics, overcoming the heterogeneity barrier.