Expression profiles analysis identifies a novel three-mRNA signature to predict overall survival in oral squamous cell carcinoma

Am J Cancer Res. 2018 Mar 1;8(3):450-461. eCollection 2018.

Abstract

Oral squamous cell carcinoma (OSCC) remains to be a challenging public health problem worldwide. However, the underlying molecular mechanism regulating the carcinogenesis of OSCC is poorly known. Gene expression profiles of GSE13601, GSE30784, GSE37991 and The Cancer Genome Atlas (TCGA) head and neck cancer were downloaded from gene expression omnibus (GEO) and TCGA database respectively. R software and bioconductor packages were used to compare and identify the differentially expressed genes (DEGs) between OSCC tissues and normal controls. The common DEGs were then subjected to gene ontology (GO) enrichment analysis, ingenuity pathway analysis (IPA), protein-protein interaction (PPI) network analysis as well as survival analysis. A total of 76 up- and 102 down-regulated DEGs were identified. Functional analysis revealed that these DEGs were associates with increased oncostatin M signaling, cell diapedesis and extravasation as well as reduced calcium signaling and loss of adherens junctions and tight junctions. A set of robust prognostic signatures including PLAU, CLDN8 and CDKN2A were identified from DEGs and could predict overall survival in OSCC patients from TCGA cohort. This three-gene signature was further successfully validated as a prognostic marker for overall survival prediction in another independent cohort GSE41613. In conclusion, our study has identified a registry of novel genes and pathways that play important roles in regulating the initiation and development of OSCC. A set of robust molecular signature is identified for prognostic prediction, which will provide useful guidance for therapeutic applications.

Keywords: Gene ontology; ingenuity pathway analysis; oral squamous cell carcinoma; protein-protein interactions network; survival analysis.