Mutational landscapes and functional insights in oral cancer and diabetes: A comparative perspective

Oral cancer and diabetes are complex diseases characterized by shared mechanisms such as oxidative stress, metabolic dysregulation, and mitochondrial dysfunction. Earlier reports have proposed that diabetes may influence oral cancer risk through modulation of the insulin receptor substrate 1 (IRS-1) and focal adhesion kinase (FAK) pathway, which contributes to tumour progression and invasion. However, their comparative mutational landscape remains underexplored. This study aims to compare mitochondrial and nuclear variants in oral cancer and diabetes to identify shared and distinct mutation profiles and their functional implications.

Public datasets from the Gene Expression Omnibus (GEO) database and additional mitochondrial sequences were analysed. Variant calling was performed using GATK Mutect2, followed by filtering with BCFtools and annotation with SnpEff. High- and moderate-impact variants were analysed across four categories: mitochondrial DNA and nuclear variants in diabetes and oral cancer. Pathway enrichment was conducted using ShinyGO with KEGG mapping, leading to the identification of both shared and condition-specific variants.

We found 49 mitochondrial variants with functional implications in the MT-ATP8, MT-ATP6, MT-ND3, and MT-ND5 genes. There were also 10,974 nuclear variants with important functional impacts. These findings highlight possible connections between metabolic stress, mitochondrial dysfunction, and oncogenic pathways, thereby providing valuable insights into the mechanisms of these diseases.

This study highlights both converging and disease-specific mutation profiles in oral cancer and diabetes. It demonstrates the value of public datasets and accessible platforms for identifying potential functional variants, which warrant further validation in larger cohorts.