Integrative Analysis of Glycosylation-Related Genes Reveals Prognostic Subtypes,Immune Evasion,and Therapeutic Vulnerabilities in Lung AdenocarcinomaOA
Background:Lung adenocarcinoma(LUAD)is the most common subtype of non-small cell lung cancer(NSCLC)and remains a leading cause of cancer-related mortality worldwide.Aberrant glycosylation contributes to tumor progression by regulating receptor signalling,immune evasion,and metastatic.However,the prognostic and therapeutic relevance of glycosylation-related genes(GRGs)in LUAD has not been comprehensively defined.Therefore,this study aimed to comprehensively evaluate GRG-associated molecular subtypes and their clinical and therapeutic relevance in LUAD.Methods:GRGs were curated from multiple public databases and integrated with transcriptomic and clinical data from The Cancer Genome Atlas LUAD cohort(TCGA-LUAD)with validation in Gene Expression Omnibus(GEO)datasets.Consensus clustering,pathway enrichment,and immune profiling were used to identify glycosylation-associated subtypes.A glycosylation activity scoring(Glyco.marker)was developed to quantify glycosylation features.Drug response prediction was analyzed using OncoPredict and the Genomics of Drug Sensitivity in Cancer(GDSC)database.Single-cell RNA sequencing(scRNA-seq)was analyzed to evaluate cell-type-specific GRG expression.Selected proteins were by immunohistochemistry(IHC)in LUAD tissue microarrays.Results:GRG expression stratified 513 LUAD patients into four molecular clusters with distinct clinical and immune characteristics.The Glyco.High group showed elevated expression of MGAT5(mannosyl(α-1,6)-glycoproteinβ-1,6-N-acetylglucosaminyltransferase),ST6GAL1(β-galactosideα-2,6-sialyltransferase 1),GALNT7(polypeptide N-acetylgalactosaminyltransferase 7),and FUT8(fucosyltransferase 8),frequent tumor protein p53(TP53)mutations,increased immune checkpoint expression,and enrichment of regulatory T cells.The Glyco.marker score predicted overall survival and was associated with stemness signatures.Drug response prediction suggested reduced sensitivity to platinum chemotherapy and epidermal growth factor receptor(EGFR)inhibitors but increased sensitivity to phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin(PI3K/AKT/mTOR)inhibitors.Conclusion:GRG-based molecular stratification identifies clinically distinct LUAD subtypes associated with immune regulation,tumor stemness,and therapeutic response.The Glyco.marker system provides a potential framework for prognostic assessment and precision oncology strategies in LUAD.
Yu-Wei Liu;Yung-Kuo Lee;Kai-Fu Chang;Chung-Bao Hsieh;Chih-Hsuan Chang;Ching-Chung Ko;Hui-Ru Lin;Chi-Jen Wu;Chien-Han Yuan;Sachin Kumar;Dahlak Daniel Solomon;Do Thi Minh Xuan;Neethu Palekkode;Ayman Fathima;Hung-Yun Lin;Chih-Yang Wang;Chih-Jen Yang;Yuen-Jung Wu
Division of Thoracic Surgery,Department of Surgery,Kaohsiung Medical University Hospital,Kaohsiung Medical University,Kaohsiung,Taiwan,ChinaMedical Laboratory,Medical Education and Research Center,Kaohsiung Armed Forces General Hospital,National Defense Medical University,Kaohsiung,Taiwan,China Division of Experimental Surgery Center,Department of Surgery,Tri-Service General Hospital,National Defense Medical University,Taipei City,Taiwan,China Institute of Medical Science and Technology,National Sun Yat-Sen University,Kaohsiung,Taiwan,ChinaMedical Laboratory,Medical Education and Research Center,Kaohsiung Armed Forces General Hospital,National Defense Medical University,Kaohsiung,Taiwan,China Division of Experimental Surgery Center,Department of Surgery,Tri-Service General Hospital,National Defense Medical University,Taipei City,Taiwan,ChinaDepartment of General Surgery,Taipei City Hospital Zhongxing Branch,Taipei City,Taiwan,ChinaMedical Laboratory,Medical Education and Research Center,Kaohsiung Armed Forces General Hospital,National Defense Medical University,Kaohsiung,Taiwan,China Institute of Medical Science and Technology,National Sun Yat-Sen University,Kaohsiung,Taiwan,ChinaDepartment of Medical Imaging,Chi-Mei Medical Center,Tainan,Taiwan,China Department of Health and Nutrition,Chia Nan University of Pharmacy and Science,Tainan,Taiwan,China School of Medicine,College of Medicine,National Sun Yat-Sen University,Kaohsiung,Taiwan,ChinaInstitute of Medical Science and Technology,National Sun Yat-Sen University,Kaohsiung,Taiwan,China Nursing Department,Kaohsiung Armed Forces General Hospital,National Defense Medical University,Kaohsiung,Taiwan,ChinaNursing Department,Kaohsiung Armed Forces General Hospital,National Defense Medical University,Kaohsiung,Taiwan,China College of Nursing,Kaohsiung Medical University,Kaohsiung,Taiwan,ChinaMedical Laboratory,Medical Education and Research Center,Kaohsiung Armed Forces General Hospital,National Defense Medical University,Kaohsiung,Taiwan,China Institute of Medical Science and Technology,National Sun Yat-Sen University,Kaohsiung,Taiwan,China Department of Otolaryngology,Kaohsiung Armed Forces General Hospital,National Defense Medical University,Kaohsiung,Taiwan,China Department of Otolaryngology,National Defense Medical University,Taipei City,Taiwan,ChinaGraduate Institute of Cancer Biology and Drug Discovery,College of Medical Science and Technology,Taipei Medical University,Taipei City,Taiwan,China Ph.D.Program for Cancer Molecular Biology and Drug Discovery,College of Medical Science and Technology,Taipei Medical University,Taipei City,Taiwan,China Faculty of Applied Sciences and Biotechnology,Shoolini University of Biotechnology and Management Sciences,Bajhol,Himachal Pradesh,IndiaGraduate Institute of Cancer Biology and Drug Discovery,College of Medical Science and Technology,Taipei Medical University,Taipei City,Taiwan,ChinaFaculty of Pharmacy,Van Lang University,69/68 Dang Thuy Tram Street,Ward 13,Binh Thanh District,Ho Chi Minh City,VietnamDepartment of Biotechnology,Mother Teresa Women’s University,Kodaikanal,Tamil Nadu,IndiaComputer Engineering with specialization in Artificial Intelligence and Machine Learning,Presidency University,Yelahanka,Bengaluru,Karnataka,IndiaDepartment of General Surgery,Taipei City Hospital Zhongxing Branch,Taipei City,Taiwan,China TMU Research Center of Cancer Translational Medicine,Taipei Medical University,Taipei City,Taiwan,China Traditional Herbal Medicine Research Center of Taipei Medical University Hospital,Taipei Medical University,Taipei City,Taiwan,China Pharmaceutical Research Institute,Albany College of Pharmacy and Health Sciences,Rensselaer,NY,USA Cancer Center,Wan Fang Hospital,Taipei Medical University,Taipei City,Taiwan,ChinaGraduate Institute of Cancer Biology and Drug Discovery,College of Medical Science and Technology,Taipei Medical University,Taipei City,Taiwan,China Ph.D.Program for Cancer Molecular Biology and Drug Discovery,College of Medical Science and Technology,Taipei Medical University,Taipei City,Taiwan,China TMU Research Center of Cancer Translational Medicine,Taipei Medical University,Taipei City,Taiwan,ChinaDivision of Pulmonary and Critical Care Medicine,Department of Internal Medicine,Kaohsiung Medical University Hospital,Kaohsiung Medical University,Kaohsiung,Taiwan,China School of Post-Baccalaureate Medicine,College of Medicine,Kaohsiung Medical University,No.100,Tzyou 1st Road,Kaohsiung,Taiwan,ChinaDepartment of Surgery,Kaohsiung Armed Forces General Hospital,National Defense Medical University,Kaohsiung,Taiwan,China
医药卫生
Lung adenocarcinomaglycosylationprognostic biomarkertumor microenvironmentimmune evasionsingle-cell RNA sequencingimmunohistochemistryprecision oncology
《Oncology Research》 2026 (7)
P.434-464,31
by Kaohsiung Armed Forces General Hospital grant No.KAFGH_D_114023 and KAFGH_D_114053。
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