Identification of miRNA-mRNA Regulatory Network and Construction of Prognostic Signature in Cervical Cancer

Abstract

Cervical cancer (CC) remains a most prevalent female cancer worldwide, but there are few biomarkers used in diagnosis and prognosis of CC. The aim of this study is to find reliable and effective biomarkers regarding CC development. Microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database to search potential miRNA-mRNA in CC. The gene ontology term enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were conducted to reveal the underlying functions and pathways of differently expressed genes (DEGs). Univariate Cox, multivariate Cox, and risk scoring methods were performed to identify a prognostic model. A total of 209 DEGs of CC were identified. In the protein-protein interaction network, hub module, and hub genes were recognized. Based on DEGs, three small molecules (thioguanosine, apigenin, and trichostatin A) were screened out as potential drugs. Two miRNAs (hsa-mir-101-3p and hsa-mir-6507-5p) and some transcription factors were found to be associated with prognosis of CC. A five-candidate gene signature (APOBEC3B, DSG2, CXCL8, ABCA8, and PLAGL1) was constructed to stratify risk subgroups for patients with CC. The risk score of the prognostic model was also found to be associated with immune cells infiltration, including mast cell activation, natural killer cells resting, dendritic cells resting, T cells regulatory (Tregs), and T cells follicular helper. The miRNA-mRNA regulatory network and the prognostic model are of great clinical significance in promoting prognosis prediction and treatment of CC.

Keywords: ceRNA; cervical cancer; differentially expressed genes; immune cells infiltration; prognostic signature.