Abstract
Objectives: Oral squamous cell carcinoma (OSCC) is the most common oral cancer with a poor prognosis owing to limited understanding of the disease mechanisms. The aim of this study was to explore and identify the potential biomarkers in OSCC by integrated bioinformatics analysis.Materials and Methods: Expression profiles of long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) were downloaded from The Cancer Genome Atlas (TCGA) and differentially expressed RNAs (DERNAs) were subsequently identified in OSCC by bioinformatics analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to analyze DERNAs. Then, the competing endogenous RNA (ceRNA) network was constructed in Cytoscape and the protein -protein interaction (PPI) network was established in the STRING database. We established a risk model to predict the overall survival of OSCC on the basis of DElncRNAs with Kaplan–Meier analysis and combined with logrank p test. Furthermore, we identified potential biomarkers by combining univariate Cox regression with overall survival rate, which were then validated in Gene Expression Omnibus (GEO), OSCC cell lines and OSCC specimens.Results: A total of 1,919 DEmRNAs, 286 DElncRNAs and 111 DEmiRNAs were found to be dysregulated in OSCC. A ceRNA network included 46 DElncRNAs,7 DEmiRNAs and 10 DEmRNAs, and the PPI network included 712 DEmRNAs including 31 hub genes. Moreover, a 7 lncRNAs risk model was established and four genes (CMA1, GNA14, HCG22, HOTTIP) were identified as biomarkers on overall survival in patients with OSCC.Conclusions: This study successfully constructed a ceRNA network and a PPI network which play a crucial role in OSCC. A risk model was established to predict the prognosis, and four DERNAs are revealed with overall survival in patients with OSCC, suggesting that they may be potential biomarkers in tumor diagnosis and treatment.
Highlights
Oral squamous cell carcinoma (OSCC) is one of the most common oral cancers worldwide [1] and has the most severe impact on the quality of life of patients
RNA expression profiles and corresponding clinical data of 316 OSCC patients and 32 normal controls were downloaded from The Cancer Genome Atlas (TCGA) database
Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used to explore the potential function of differentially expressed RNAs (DERNAs)
Summary
Oral squamous cell carcinoma (OSCC) is one of the most common oral cancers worldwide [1] and has the most severe impact on the quality of life of patients. Medical equipment and treatment methods are more advanced in recently years, the 5-year overall survival rate of OSCC remains only 40–50% [3] on account of relatively low responsiveness to treatment, severe drug resistance [4], diagnosis at terminal stage, etc., whereas the 5-year overall survival rate can rise markedly to more than 85% in patients diagnosed with early-staged tumors [5]. Early diagnosis is very important for improving the prognosis of patients with OSCC. Recent research demonstrated that lncRNA combined with mRNA biomarkers may improve diagnosis [9]. There are fewer effective lncRNAs and mRNAs biomarkers used for diagnosis in OSCC
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