Novel Prognostic Biomarkers for Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (CESC) Patients via Analysis of Competing Endogenous RNA (ceRNA) Network

Abstract

Background. Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is a common malignant gynecological cancer. The ceRNA networks play important roles in many tumors, while RILPL2-related ceRNA network has been seldom studied in CESC. Methods. All CESC data was obtained from TCGA database. Differentially expressed RNAs and predicted target RNAs were cross analyzed to construct ceRNA network. RNA and clinicopathological characteristics’ influence on overall survival (OS) were determined by univariate and multivariate Cox regression analyses. Lasso regression was used to construct the prediction model. Coexpression analysis was performed to explore the association of gene expression with CESC. This was followed by an experimental validation based on these results. Results. Between high and low RILPL2 expression CESC patients, totally 1227 DEmRNAs, 39 DEmiRNAs, and 1544 DElncRNAs were identified. After multiple cross analyses, 1 miRNA hsa-miR-1293, 20 mRNAs, and 43 lncRNAs were maintained to construct ceRNA network. CADM3-AS1, LINC00092, and ZNF667-AS1 in ceRNA network were significantly associated with the OS of CESC patients, and patients with low expression of these lncRNAs had worse prognosis. Significant lower expressions of these lncRNAs were also observed in CESC cell line compared with normal cell line. Conclusion. Low expressions of CADM3-AS1, LINC00092, and ZNF667-AS1 in ceRNA network were probably promising poor prognostic biomarkers for CESC patients. The genes show a prospective research area for CESC-targeted treatment in the future.