Genomic, transcriptomics, and epigenomic alterations in AREG gene in LUSC and HNSCC

Objectives

Cancers of the head and neck region and lungs share similar risk factors. The increased prevalence of these two cancer types underscores the need to identify diagnostic, therapeutic, and prognostic biomarkers for their management. In this context, the present study aims to identify genetic alterations in the AREG gene and their possible association with HNSCC and LUSC.

Methods

The study employed a computational design, utilizing the following databases and tools to identify the association between disease phenotypes and genes. The cBioPortal database was used to analyze genetic alterations in the AREG gene across TCGA datasets for HNSCC and LUSC. The survival probability and gene expression profile were analyzed using UALCAN. Welch's test demonstrated the statistical significance between the normal and tumor tissues. The microRNA targets of AREG were assessed using the miRDB.

Results

The AREG gene presented with less than 1 % alteration in HNSCC and 4 % in LUSC. Interestingly, a significant upregulation of the AREG gene was observed in HNSCC patients, whereas downregulation was noted in LUSC. The increased gene expression profile correlated well with a poor prognosis in HNSCC patients, while low expression was associated with a good prognosis in LUSC patients. Experimental validation of OSCC samples revealed a decrease in gene expression compared to normal samples. Furthermore, the microRNAs hsa-miR-1185-1 and hsa-miR-487b were identified as potential targets of AREG, influencing the survival of patients with HNSCC.

Conclusions

The overexpression of AREG in HNSCC, along with its poor prognosis, highlights the oncogenic role played by this gene. Interestingly, the epigenetic component, specifically microRNAs hsa-miR-1185-1 and hsa-miR-487b, was found to be downregulated, suggesting their influence on AREG expression. These findings require further validation through functional studies to elucidate the association between AREG and the cancer phenotype.