Identification of Co-Expression Modules and Genes Associated With Tumor Progression in Oral Squamous Cell Carcinoma

Abstract

Oral squamous cell carcinoma (OSCC) is a common head-and-neck cancer with a deficiency of early diagnosis and poor prognosis. To identify potential diagnostic and prognostic markers of OSCC, we firstly used weighted gene co-expression network analysis (WGCNA) to build a co-expression module from GSE42743. Next, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on specified units from selected modules utilizing Database for Annotation, Visualization, and Integrated Discovery (DAVID). Additionally, we identified and validate hub genes of these specified modules from multiple datasets like GEPIA and TCGA. In total 16 co-expression modules were built by 17,238 genes of 74 tumor samples utilizing WGCNA. Through pathway and functional enrichment analysis, the turquoise module was most firmly relevant to the cell cycle, oocyte meiosis, and p53 signaling pathway. Hub genes VRK1, NUP37, HMMR, SPC25, and RUVBL1 were identified to be related to oral cancer at both molecular level and clinical levels. The expressions of these genes differed in tumor tissues and normal tissues. Meanwhile, patients with high hub gene expression had a poor prognosis clinically. To conclude, five hub genes were identified to be relevant to oral cancer from the molecular level and the clinical level. Therefore, the detection of these genes was of great significance. They can be regarded as diagnostic and prognostic biomarkers for oral cancer. Also, they could shed light on the improvement of patients’ overall survival and prognosis, which needs further analysis in the future.

MicroRNA-Based Markers of Oral Tongue Squamous Cell Carcinoma and Buccal Squamous Cell Carcinoma: A Systems Biology Approach

“…Subsequently, Sun et al [ 56 ] used the GEPIA web server to validate their experimental results; this included evaluating the mRNA expression levels of AKT1 and PLK1 in HNSCC than in healthy tissues and analyzing the prognostic effect of the genes in patients with HNSCC. Fang et al [ 57 ] identified several genes with a correlation score >0.8 in a PPI network associated with the pathogenesis of OSCC. Next, the authors used the GEPIA tool to evaluate the prognostic role of the genes in HNSCC.…”

The role of VRK1 in chromatin remodeling: regulation of histone post-translational modifications and epigenetic enzymes

“…Overexpression of VRK1, detected using microarray transcriptomic platforms, is associated with poor prognosis of cancer such as breast 141 , lung 142,143 , head and neck squamous cell carcinomas 127 , colon 144 , liver 145 , gliomas 146,147 , multiple myeloma 148 , esophageal carcinomas 149 , and oral cancer 150 . For example, VRK1 expression positively correlates with glioma pathological grade and its depletion in glioblastoma cells alters DDR and promotes tumor cells death 146,151 .…”

“…Briefly, the role of VRK1 in cancer epigenetics is still unclear and requires further research, but it is known that VRK1 overexpression is related to poor prognosis in many tumor types such as breast, lung, head and neck squamous cell carcinomas, colon, liver, gliomas, multiple myeloma, esophageal carcinomas, and oral cancer 127,[141][142][143][144][145][146][147][148][149][150] . This makes VRK1 a good candidate to target from an epigenetic therapeutic approach.…”