Novel Autophagy-Related Gene Signature Investigation for Patients With Oral Squamous Cell Carcinoma

Abstract

The correlation between autophagy defects and oral squamous cell carcinoma (OSCC) has been previously studied, but only based on a limited number of autophagy-related genes in cell lines or animal models. The aim of the present study was to analyze differentially expressed autophagy-related genes through The Cancer Genome Atlas (TCGA) database to explore enriched pathways and potential biological function. Based on TCGA database, a signature composed of four autophagy-related genes (CDKN2A, NKX2-3, NRG3, and FADD) was established by using multivariate Cox regression models and two Gene Expression Omnibus datasets were applied for external validation. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to study the function of autophagy-related genes and their pathways. The most significant GO and KEGG pathways were enriched in several key pathways that were related to the progression of autophagy and OSCC. Furthermore, a prognostic risk score was constructed based on the four genes; patients were then divided into two groups (i.e., high risk and low risk) in terms of the median of risk score. Prognosis of the two groups and results showed that patients at the low-risk group had a much better prognosis than those at the high-risk group, regardless of whether they were in the training datasets or validation datasets. Multivariate Cox regression results indicated that the risk score of the autophagy-related gene signatures could greatly predict the prognosis of patients after controlling for several clinical covariates. The findings of the present study revealed that autophagy-related gene signatures play an important role in OSCC and are potential prognostic biomarkers and therapeutic targets.