دورية أكاديمية
A systematic pan-cancer analysis identifies LDHA as a novel predictor for immunological, prognostic, and immunotherapy resistance.
العنوان: | A systematic pan-cancer analysis identifies LDHA as a novel predictor for immunological, prognostic, and immunotherapy resistance. |
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المؤلفون: | Zhang Q; The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, P.R. China.; Southwest Medical University, Luzhou, P.R. China., Luo Y; The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, P.R. China.; Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, P.R. China., Qian B; Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, P.R. China.; School of Pharmacy, Henan University, Kaifeng, P.R. China., Cao X; Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, P.R. China., Xu C; Southwest Medical University, Luzhou, P.R. China., Guo K; The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, P.R. China.; Southwest Medical University, Luzhou, P.R. China., Wan R; The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, P.R. China.; Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, P.R. China., Jiang Y; Southwest Medical University, Luzhou, P.R. China., Wang T; Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, P.R. China., Mei Z; The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, P.R. China.; Southwest Medical University, Luzhou, P.R. China., Liu J; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, P.R. China., Lv C; The Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, P.R. China.; Southwest Medical University, Luzhou, P.R. China.; Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, P.R. China. |
المصدر: | Aging [Aging (Albany NY)] 2024 May 03; Vol. 16 (9), pp. 8000-8018. Date of Electronic Publication: 2024 May 03. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Impact Journals, LLC Country of Publication: United States NLM ID: 101508617 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1945-4589 (Electronic) Linking ISSN: 19454589 NLM ISO Abbreviation: Aging (Albany NY) Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Albany, NY : Impact Journals, LLC |
مواضيع طبية MeSH: | Tumor Microenvironment*/immunology , Immunotherapy* , Neoplasms*/immunology , Neoplasms*/genetics , Neoplasms*/therapy , Drug Resistance, Neoplasm*/genetics, Humans ; Prognosis ; Biomarkers, Tumor/metabolism ; Biomarkers, Tumor/genetics ; Gene Expression Regulation, Neoplastic ; L-Lactate Dehydrogenase/metabolism ; L-Lactate Dehydrogenase/genetics ; Cell Line, Tumor |
مستخلص: | Lactate dehydrogenase A (LDHA), a critical enzyme involved in glycolysis, is broadly involved multiple biological functions in human cancers. It is reported that LDHA can impact tumor immune surveillance and induce the transformation of tumor-associated macrophages, highlighting its unnoticed function of LDHA in immune system. However, in human cancers, the role of LDHA in prognosis and immunotherapy hasn't been investigated. In this study, we analyzed the expression pattern and prognostic value of LDHA in pan-cancer and explored its association between tumor microenvironment (TME), immune infiltration subtype, stemness scores, tumor mutation burden (TMB), and immunotherapy resistance. We found that LDHA expression is tumor heterogeneous and that its high expression is associated with poor prognosis in multiple human cancers. In addition, LDHA expression was positively correlated with the presence of mononuclear/macrophage cells, and also promoted the infiltration of a range of immune cells. Genomic alteration of LDHA was common in different types of cancer, while with prognostic value in pan-cancers. Pan-cancer analysis revealed that the significant correlations existed between LDHA expression and tumor microenvironment (including stromal cells and immune cells) as well as stemness scores (DNAss and RNAss) across cancer types. Drug sensitivity analysis also revealed that LDHA was able to predict response to chemotherapy and immunotherapy. Furthermore, it was confirmed that knockdown of LDHA reduced proliferation and migration ability of lung cancer cells. Taken together, LDHA could serve as a prognostic biomarker and a potential immunotherapy marker. |
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فهرسة مساهمة: | Keywords: LDHA; immunotherapy; pan-cancer; single-cell RNA-Seq; tumor microenvironment |
المشرفين على المادة: | 0 (LDHA protein, human) |
تواريخ الأحداث: | Date Created: 20240506 Date Completed: 20240520 Latest Revision: 20240703 |
رمز التحديث: | 20240703 |
مُعرف محوري في PubMed: | PMC11132014 |
DOI: | 10.18632/aging.205800 |
PMID: | 38709280 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1945-4589 |
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DOI: | 10.18632/aging.205800 |