A comprehensive and systematic analysis of Dihydrolipoamide S-acetyltransferase as a novel prognostic biomarker in pan-cancer and glioma.

BACKGROUND

Dihydrolipoamide S-acetyltransferase () is a subunit of the pyruvate dehydrogenase complex (PDC), a rate-limiting enzyme complex, that can participate in either glycolysis or the tricarboxylic acid cycle (TCA). However, the pathogenesis is not fully understood. We aimed to perform a more systematic and comprehensive analysis of in the occurrence and progression of tumors, and to investigate its function in patients' prognosis and immunotherapy.

METHODS

The differential expression, diagnosis, prognosis, genetic and epigenetic alterations, tumor microenvironment, stemness, immune infiltration cells, function enrichment, single-cell analysis, and drug response across cancers were conducted based on multiple computational tools. Additionally, we validated its carcinogenic effect and possible mechanism in glioma cells.

RESULTS

We exhibited that expression was increased in most tumors, especially in glioma, and affected the survival of tumor patients. was related to RNA modification genes, DNA methylation, immune infiltration, and immune infiltration cells, including CD4+ T cells, CD8+ T cells, Tregs, and cancer-associated fibroblasts. Single-cell analysis displayed that might regulate cancer by mediating angiogenesis, inflammation, and stemness. Enrichment analysis revealed that might take part in the cell cycle pathway. Increased expression of leads tumor cells to be more resistant to many kinds of compounds, including PI3Kβ inhibitors, PKC inhibitors, HSP90 inhibitors, and MEK inhibitors. In addition, glioma cells with silence inhibited proliferation, migration, and invasion ability, and promoted cell apoptosis.

CONCLUSION

We conducted a comprehensive analysis of in the occurrence and progression of tumors, and its possible functions and mechanisms. is a potential diagnostic, prognostic, and immunotherapeutic biomarker for cancer patients.