{"title":"A comprehensive and systematic analysis of Dihydrolipoamide S-acetyltransferase <i>(DLAT)</i> as a novel prognostic biomarker in pan-cancer and glioma.","authors":"Hui Zhou, Zhengyu Yu, Jing Xu, Zhongwang Wang, Yali Tao, Jinjin Wang, Peipei Yang, Jinrong Yang, Ting Niu","doi":"10.32604/or.2024.048138","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"32 12","pages":"1903-1919"},"PeriodicalIF":2.0000,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11576973/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oncology Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.32604/or.2024.048138","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
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Abstract
Background: Dihydrolipoamide S-acetyltransferase (DLAT) 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 DLAT 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 DLAT expression was increased in most tumors, especially in glioma, and affected the survival of tumor patients. DLAT 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 DLAT might regulate cancer by mediating angiogenesis, inflammation, and stemness. Enrichment analysis revealed that DLAT might take part in the cell cycle pathway. Increased expression of DLAT 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 DLAT silence inhibited proliferation, migration, and invasion ability, and promoted cell apoptosis.
Conclusion: We conducted a comprehensive analysis of DLAT in the occurrence and progression of tumors, and its possible functions and mechanisms. DLAT is a potential diagnostic, prognostic, and immunotherapeutic biomarker for cancer patients.
期刊介绍：
Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.
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