Integrative Multi-Omics Analysis Reveals Candidate Biomarkers for Oral Squamous Cell Carcinoma

Oral squamous cell carcinoma (OSCC) is one of the most common types of cancer worldwide. Due to the lack of early detection and treatment, the survival rate of OSCC remains poor and the incidence of OSCC has not decreased during the past decades. To explore potential biomarkers and therapeutic targets for OSCC, we analyzed differentially expressed genes (DEGs) associated with OSCC using RNA sequencing technology. Methylation-regulated and differentially expressed genes (MeDEGs) of OSCC were further identified via an integrative approach by examining publicly available methylomic datasets together with our transcriptomic data. Protein-protein interaction (PPI) networks of MeDEGs were constructed and highly connected hub MeDEGs were identified from these PPI networks. Subsequently, expression and survival analyses of hub genes were performed using The Cancer Genome Atlas (TCGA) database and the Gene Expression Profiling Interactive Analysis (GEPIA) online tool. A total of 56 upregulated MeDEGs and 170 downregulated MeDEGs were identified in OSCC. Eleven hub genes with high degree of connectivity were picked out from the PPI networks constructed by those MeDEGs. Among them, the expression level of four hub genes (CTLA4, CDSN, ACTN2, and MYH11) were found to be significantly changed in the head and neck squamous carcinoma (HNSC) patients. Three hypomethylated hub genes (CTLA4, GPR29, and TNFSF11) and one hypermethylated hub gene (ISL1) were found to be significantly associated with overall survival (OS) of HNSC patients. Therefore, these hub genes may serve as potential DNA methylation biomarkers and therapeutic targets of OSCC.