A novel four-gene prognostic signature as a risk biomarker in cervical cancer

Abstract

Background: Cervical cancer (CC) is a major malignancy affecting women worldwide, with limited treatment options for patients with advanced disease. The aim of this study was to identify novel prognostic biomarkers for CC by a bioinformatics-based analysis using the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA)-CC cohort. Methods: RNA-Seq data from four GEO datasets (GSE5787, GSE6791, GSE26511, and GSE63514) were used to identify differentially expressed genes (DEGs) between CC and normal cervical tissues. Functional and enrichment analyses of the DEGs were performed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and the Database for Annotation, Visualization and Integrated Discovery (DAVID). The Oncomine database, Cytoscape software, and Kaplan–Meier survival analysis were used for in-depth screening for hub DEGs. Cox regression was then used to develop prognostic signature, which was in turn used to create a nomogram. Results: A total of 207 DEGs were identified in the tissue samples, eight of which were prognostically significant in terms of overall survival (OS). Thereafter, a novel four-gene signature consisting of DSG2, MMP1, SPP1, and MCM2 was developed and validated using stepwise Cox analysis. The area under the receiver operating characteristic (ROC) curve (AUC) values of 0.785, 0.609, and 0.686 in the training, verification, and combination groups, respectively. Moreover, the nomogram analysis showed that a combination of this four-gene signature plus lymph node metastasis (LNM) status effectively predicted the 1- and 3-year OS probabilities of CC patients with accuracies of 69.01% and 83.93%, respectively. Conclusions: We developed a four-gene signature that can accurately predict the prognosis, in terms of OS, of CC patients, and could be a valuable tool for designing treatment strategies.

Prognostic Role of Matrix Metalloproteinases in Cervical Cancer: A Meta-Analysis

“…Roszik et al 38 revealed MMP-1 was overexpressed in cervical cancer, and knockdown of MMP-1 reduced the proliferation and migration of cervical cancers. Wang et al 39 proposed MMP-1 as a risk factor in cervical cancer.…”

“…Therefore, we carried out this meta-analysis to evaluate the correlation between MMPs and prognosis in cervical cancer. 25-41…”

“…Therefore, we carried out this meta-analysis to evaluate the correlation between MMPs and prognosis in cervical cancer. [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41]…”

Expression Profiles Reveal Involvement of VEGF, IGF1, BIRC5, and MMP1 in Vulvar Carcinogenesis

“…Kaplan Meier Plotter was utilized to determine the prognostic values of IGF1, BIRC5, VEGF, and MMP1, which showed that increased IGF1 or BIRC5 expression correlated with better survival, while increased VEGF or MMP1 expression correlated with poorer survival in cervical carcinoma patients (Supplementary Material). Previous studies have consistently reported [14][15][16][17][18] that VEGF, MMP1 and BIRC5 gene expression is up-regulated and IGF1 expression is down-regulated in both cervical and vulvar tumors. We also performed follow-up and survival analyses, which showed that the 4 genes had statistically insignificant prognostic value in VSCC, which may be due to the insufficient sample size and the short follow-up time of some cases.…”