Construction and analysis of a competing endogenous RNA network to reveal potential prognostic biomarkers for Oral Floor Squamous Cell Carcinoma.

Wenjing Zhang,Laner Shi,Zhangzhi Zhu,Shuai Xu,Xinying Xie,Esra Bozgeyik

doi:10.1371/journal.pone.0238420

Abstract

BackgroundPatients diagnosed with Oral Floor Squamous Cell Carcinoma (OFSCC) face considerable challenges in physiology and psychology. This study explored prognostic signatures to predict prognosis in OFSCC through a detailed transcriptomic analysis.MethodWe built an interactive competing endogenous RNA (ceRNA) network that included lncRNAs, miRNAs and mRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to predict the gene functions and regulatory pathways of mRNAs. Least absolute shrinkage and selection operator algorithm (LASSO) analysis and Cox regression analysis were used to screen prognosis factors. The Kaplan-Meier method was used to analyze the survival rate of prognosis factors. Risk score was used to assess the reliability of the prediction model.ResultsA specific ceRNA network consisting of 56 mRNAs, 16 miRNAs and 31 lncRNAs was established. Three key genes (HOXC13, TGFBR3, KLHL40) and 4 clinical factors (age, gender, TNM, and clinical stage) were identified and effectively predicted the for survival time. The expression of a gene signature was validated in two external validation cohorts. The signature (areas under the curve of 3 and 5 years were 0.977 and 0.982, respectively) showed high prognostic accuracy in the complete TCGA cohort.ConclusionsOur study successfully developed an extensive ceRNA network for OFSCC and further identified a 3-mRNA and 4-clinical-factor signature, which may serve as a biomarker.

Highlights

Oral cancer is one of the most common malignant tumors of the head and neck [1]
A specific competitive endogenous RNA (ceRNA) network consisting of 56 mRNAs, 16 miRNAs and 31 lncRNAs was established
Our study successfully developed an extensive ceRNA network for Oral Floor Squamous Cell Carcinoma (OFSCC) and further identified a 3-mRNA and 4-clinical-factor signature, which may serve as a biomarker

Summary

Introduction

Oral cancer is one of the most common malignant tumors of the head and neck [1]. 10% of patients with advanced metastatic oral cancer survive for 5 years following therapy [2]. The incidence of Oral Floor Squamous Cell Carcinoma (OFSCC) is only inferior to tongue cancer. MiRNA combined with targeted mRNA and render it untranslatable normally, silencing the corresponding genes. In 2011, Salmena [4] proposed the competitive endogenous RNA (ceRNA) hypothesis, which states that lncRNA could combine competitively with miRNAs, eliminating the inhibition of miRNAs on target genes and regulating the expression of target genes. Patients diagnosed with Oral Floor Squamous Cell Carcinoma (OFSCC) face considerable challenges in physiology and psychology. This study explored prognostic signatures to predict prognosis in OFSCC through a detailed transcriptomic analysis.

Methods

Results

Conclusion