Deciphering the Genetic Alteration in the ZEB2 Gene Network and Their Possible Association With Head and Neck Squamous Cell Carcinoma (HNSCC)

Cureus. 2023 Oct 3;15(10):e46440. doi: 10.7759/cureus.46440. eCollection 2023 Oct.

Abstract

Background Head and neck squamous cell carcinoma (HNSCC) is an abnormal growth of cells that leads to tumor formation in the head and neck region. Several genes and genetic networks are involved in the process of carcinogenesis. Aim The aim of the present study is to unravel the prognostic marker from a pool of interacting networks governed by the ZEB2gene. Materials and methods Computational analysis was employed to identify the protein network interactions, genetic alterations, gene expression, and the survival analysis of the ZEB2 dysregulated network in the head and neck cancer dataset (HNSCC) from the Cancer Genome Atlas (TCGA), Firehose Legacy. The gene expression profiling and survival analysis were performed for the gene with the highest frequency of genetic alteration. Result The interaction network returned nine genes that interact with ZEB2. The ARHGAP31 gene was found to harbor the highest frequency of alteration at the genomic as well as the transcriptomic levels. Survival was also found to be significant with respect to the differential gene expression pattern while comparing the genders and different ethnic groups. Females with higher expression of ARHGAP31 and the Asian population exhibiting low/medium expression of the same were found to present with poor survival probability. Conclusion The identification of putative drivers or a candidate gene of a network could provide clues about the association with the disease phenotype of HNSCC. The present study identifies ARHGAP31 as the key gene of the ZEB2 gene network, wherein the genetic alterations correlate with the transcriptomics data and the survival probability of patients segregated based on gender and race. Further experimental evaluation is warranted to confirm the association of this infamous gene ARHGAP31 with the development of oral carcinoma.

Keywords: gene expression profile; human population genetics; oral cancers; somatic mutations; survival analysis.