@Article{or.2024.048138,
AUTHOR = {HUI ZHOU, ZHENGYU YU, JING XU, ZHONGWANG WANG, YALI TAO, JINJIN WANG, PEIPEI YANG, JINRONG YANG, TING NIU},
TITLE = {A comprehensive and systematic analysis of Dihydrolipoamide S-acetyltransferase <i>(DLAT)</i> as a novel prognostic biomarker in pan-cancer and glioma},
JOURNAL = {Oncology Research},
VOLUME = {32},
YEAR = {2024},
NUMBER = {12},
PAGES = {1903--1919},
URL = {http://www.techscience.com/or/v32n12/58610},
ISSN = {1555-3906},
ABSTRACT = { <b>Background:</b> Dihydrolipoamide S-acetyltransferase (<i>DLAT</i>) 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 <i>DLAT</i> in the occurrence and progression of tumors, and to investigate its function in patients’ prognosis and immunotherapy. <b>Methods:</b> 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. <b>Results:</b> We exhibited that <i>DLAT</i> expression was increased in most tumors, especially in glioma, and affected the survival of tumor patients. <i>DLAT</i> 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 <i>DLAT</i> might regulate cancer by mediating angiogenesis, inflammation, and stemness. Enrichment analysis revealed that <i>DLAT</i> might take part in the cell cycle pathway. Increased expression of <i>DLAT</i> 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 <i>DLAT</i> silence inhibited proliferation, migration, and invasion ability, and promoted cell apoptosis. <b>Conclusion:</b> We conducted a comprehensive analysis of <i>DLAT</i> in the occurrence and progression of tumors, and its possible functions and mechanisms. <i>DLAT</i> is a potential diagnostic, prognostic, and immunotherapeutic biomarker for cancer patients.},
DOI = {10.32604/or.2024.048138}
}