Integration of eQTL and multi-omics comprehensive analysis of triacylglycerol synthase 1 (TGS1) as a prognostic and immunotherapeutic biomarker across pan-cancer

Abstract

An increasing number of expression quantitative trait loci (eQTLs) have been linked to tumorigenesis. In this study, we used Mendelian randomization (MR) to identify a novel cancer susceptibility gene, Trimethylguanosine Synthase 1 (TGS1). TGS1-induced hypermethylation at the 5' end of human telomerase RNA (hTR) impedes hTR accumulation, decreasing telomerase assembly factor levels and thus limiting telomere elongation, a crucial factor in tumor progression. Despite its significant role in cancer development, the TGS1-cancer relationship requires further experimental validation and bioinformatics analysis. To bridge this knowledge gap, we performed a comprehensive pan-cancer study using MR to evaluate TGS1's involvement in cancer progression. Leveraging data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), we analyzed TGS1's role in 33 tumor types. The results indicated higher TGS1 expression in most tumors, with a significant correlation to patient prognosis. We also noted variations in TGS1 phosphorylation at different sites and a strong link between TGS1 expression and the infiltration of various immune cells. In addition, our enrichment analysis of TGS1-associated genes shed light on the molecular mechanisms involved. The study also highlighted TGS1's significant role in cellular apoptosis. Overall, our findings offer an in-depth analysis of TGS1's oncogenic roles across multiple tumor types and underscore its potential as an oncogene, biomarker, and gene therapy target in diverse cancers.

Keywords: Apoptosis; Mendelian randomization study; TGS1; TME; pan-cancer.