Abstract
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.
Highlights
Oral squamous cell carcinoma (OSCC) is the seventh most common cancer in males under the age of 60, with about 400,000 new cases reported annually worldwide [1]
Principal component analysis (PCA) of RNA−seq data showed that deconvoluted data from OSCC samples and normal adjacent tissue (NAT) were clustered into different patterns (Figure 1A), suggesting the underlying differences between these two conditions
Further functional clustering analysis using the online tools in Metascape shown that upregulated genes were mainly involved in functions such as response to bacterium, formation of the cornified envelope, extracellular matrix organization, antimicrobial humoral response, etc. (Figure 1C), while downregulated genes were mainly involved in muscle system process, muscle contraction, muscle structure development, muscle cell development, etc. (Figure 1D)
Summary
Oral squamous cell carcinoma (OSCC) is the seventh most common cancer in males under the age of 60, with about 400,000 new cases reported annually worldwide [1]. The incidences of OSCC in developing countries like India and Brazil could be more than tenfold higher than those in Western countries. OSCC is predominantly seen in male over the age of 65, the disease. Identifying Candidate Biomarkers for OSCC appears to be increasing in younger patients under the age of 45 and the gender difference has been decreasing over the past few decades. OSCC represents a major public health problem, especially in poor and developing countries. Under the standard treatment plan, the outcomes of patients with OSCC could be completely different [2, 3]. Uncovering the complex molecular changes leading to the development of OSCC as well as the factors contributing to the differential prognosis among OSCC patients represents a continuingly unmet medical need
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