The malignant neoplasm of the cervix, cervical cancer, has effects on the reproductive tract. Although infection with oncogenic human papillomavirus is essential for cervical cancer development, it alone is insufficient to explain the development of cervical cancer. Therefore, other risk factors such as host genetic factors should be identified, and their importance in cervical cancer induction should be determined. Although gene expression profiling studies in the last decade have made significant molecular findings about cervical cancer, adequate screening and effective treatment strategies have yet to be achieved. In the current study, researchers from Marmara University performed meta-analysis on cervical cancer-associated transcriptome data and reporter biomolecules were identified at RNA (mRNA, miRNA), protein (receptor, transcription factor, etc.), and metabolite levels by the integration of gene expression profiles with genome-scale biomolecular networks. This approach revealed already-known biomarkers, tumor suppressors and oncogenes in cervical cancer as well as various receptors (e.g. ephrin receptors EPHA4, EPHA5, and EPHB2; endothelin receptors EDNRA and EDNRB; nuclear receptors NCOA3, NR2C1, and NR2C2), miRNAs (e.g., miR-192-5p, miR-193b-3p, and miR-215-5p), transcription factors (particularly E2F4, ETS1, and CUTL1), other proteins (e.g., KAT2B, PARP1, CDK1, GSK3B, WNK1, and CRYAB), and metabolites (particularly, arachidonic acids) as novel biomarker candidates and potential therapeutic targets. The differential expression profiles of all reporter biomolecules were cross-validated in independent RNA-Seq and miRNA-Seq datasets, and the prognostic power of several reporter biomolecules, including KAT2B, PCNA, CD86, miR-192-5p and miR-215-5p was also demonstrated. In this study, we reported valuable data for further experimental and clinical efforts, because the proposed biomolecules have significant potential as systems biomarkers for screening or therapeutic purposes in cervical carcinoma
Meta-analysis of the transcriptome datasets associated with cervical cancer
(A) Venn diagram representing the distribution of the down-regulated transcripts in the datasets, where 113 transcripts were mutually down-regulated in all datasets (i.e., down-regulated core genes). (B) Venn diagram representing the distribution of the up-regulated transcripts in datasets, where 199 transcripts were mutually up-regulated in all datasets (i.e., up-regulated core genes). (C) The clustering of the proteins encoded by the down-regulated core genes of cervical cancer according to their molecular activities. (D) The clustering of the proteins encoded by the up-regulated core genes of cervical cancer according to their molecular activities (DEGs: differentially expressed genes).The gene set overrepresentation analysis of the core genes based on the annotations stored in KEGG and GAD databases resulted in (particularly cancers), p53 signaling, and pyrimidine metabolism . Periodontitis, hypospadias, and arterial blood pressure pathways were down-regulated, whereas up-regulated core genes were enriched in those associated with the cell cycle, DNA replication, oocyte meiosis, several cancers (colorectal, bladder, breast, ovarian, lung, stomach, and prostate), autoimmune disorders (including rheumatoid arthritis and systemic lupus erythematosus), Alzheimer’s disease, p53 signaling pathway, and pyrimidine metabolism.