Downregulation of Glycine N-Acyltransferase in Kidney Renal Clear Cell Carcinoma: A Bioinformatic-Based Screening

Abstract

Clear cell renal cell carcinoma (KIRC) is the most common subtype of renal cell carcinoma (RCC). This form of cancer is characterized by resistance to traditional therapies and an increased likelihood of metastasis. A major factor contributing to the pathogenesis of KIRC is the alteration of metabolic pathways. As kidney cancer is increasingly considered a metabolic disease, there is a growing need to understand the enzymes involved in the regulation of metabolism in tumorigenic cells. In this context, our research focused on glycine N-acyltransferase (GLYAT), an enzyme known to play a role in various metabolic diseases and cancer. Here, through a bioinformatic analysis of public databases, we performed a characterization of GLYAT expression levels in KIRC cases. Our goal is to evaluate whether GLYAT could serve as a compelling candidate for an in-depth study, given its pivotal role in metabolic regulation and previously established links to other malignancies. The analysis showed a marked decrease in GLYAT expression in all stages and grades of KIRC, regardless of mutation rates, suggesting an alternative mechanism of regulation along the tumor development. Additionally, we observed a hypomethylation in the GLYAT promoter region and a negative correlation between the expression of the GLYAT and the levels of cancer-associated fibroblasts. Finally, the data show a correlation between higher levels of GLYAT expression and better patient prognosis. In conclusion, this article underscores the potential of GLYAT as a diagnostic and prognostic marker in KIRC.