Lactylation-related gene signatures identify glioma molecular subtypes with prognostic, immunological, and therapeutic implications

IntroductionLactic acid is a by-product of energy metabolism and a signaling molecule that influences tumor progression by regulating immune cell function, angiogenesis, and epigenetic modifications.MethodsThis study analyzed data from the TCGA database on gliomas to systematically elucidate the exp...

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Main Authors: Yanliang Tang, Xiaoli Zhang, Xiaofei Tang, Ye Yuan, Wenwen Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1613423/full
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author Yanliang Tang
Xiaoli Zhang
Xiaofei Tang
Ye Yuan
Wenwen Wang
author_facet Yanliang Tang
Xiaoli Zhang
Xiaofei Tang
Ye Yuan
Wenwen Wang
author_sort Yanliang Tang
collection DOAJ
description IntroductionLactic acid is a by-product of energy metabolism and a signaling molecule that influences tumor progression by regulating immune cell function, angiogenesis, and epigenetic modifications.MethodsThis study analyzed data from the TCGA database on gliomas to systematically elucidate the expression patterns, prognostic value, and functional regulatory networks of lactylation-related genes.ResultsIn this study, 17 lactylation-related prognostic genes were identified through the analysis of TCGA-GBM data. Using non- negative matrix factorization (NMF), two GBM subtypes based on lactylation- related genes (LRGs), termed GBM1 and GBM2, were identified. Survival analysis revealed that the overall survival (OS) of the GBM1 group was significantly lower than that of GBM2 group. Furthermore, notable differences were observed in the expression of key GBM-associated molecular markers between the two subtypes. Tumor microenvironment (TME) analysis demonstrated distinct immune landscapes and genomic characteristics between GBM1 and GBM2. The GBM1 group exhibited higher immune cell infiltration and immune function scores compared to GBM2. Drug sensitivity analysis further revealed differences in response to chemotherapy and targeted therapies between the two subtypes. In vitro data demonstrated that LCP1 knockdown suppressed cell proliferation and invasion, and promoted apoptosis in glioma cells.ConclusionIn conclusion, our study systematically uncovers the significant role of LRGs in GBM molecular subtyping, prognosis evaluation, and therapeutic guidance. These findings offer new insights and potential strategies for the personalized treatment of GBM.
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spelling doaj-art-92528671b07b4feb9c4d4ffd52bf0af02025-08-20T03:13:32ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-07-011510.3389/fonc.2025.16134231613423Lactylation-related gene signatures identify glioma molecular subtypes with prognostic, immunological, and therapeutic implicationsYanliang TangXiaoli ZhangXiaofei TangYe YuanWenwen WangIntroductionLactic acid is a by-product of energy metabolism and a signaling molecule that influences tumor progression by regulating immune cell function, angiogenesis, and epigenetic modifications.MethodsThis study analyzed data from the TCGA database on gliomas to systematically elucidate the expression patterns, prognostic value, and functional regulatory networks of lactylation-related genes.ResultsIn this study, 17 lactylation-related prognostic genes were identified through the analysis of TCGA-GBM data. Using non- negative matrix factorization (NMF), two GBM subtypes based on lactylation- related genes (LRGs), termed GBM1 and GBM2, were identified. Survival analysis revealed that the overall survival (OS) of the GBM1 group was significantly lower than that of GBM2 group. Furthermore, notable differences were observed in the expression of key GBM-associated molecular markers between the two subtypes. Tumor microenvironment (TME) analysis demonstrated distinct immune landscapes and genomic characteristics between GBM1 and GBM2. The GBM1 group exhibited higher immune cell infiltration and immune function scores compared to GBM2. Drug sensitivity analysis further revealed differences in response to chemotherapy and targeted therapies between the two subtypes. In vitro data demonstrated that LCP1 knockdown suppressed cell proliferation and invasion, and promoted apoptosis in glioma cells.ConclusionIn conclusion, our study systematically uncovers the significant role of LRGs in GBM molecular subtyping, prognosis evaluation, and therapeutic guidance. These findings offer new insights and potential strategies for the personalized treatment of GBM.https://www.frontiersin.org/articles/10.3389/fonc.2025.1613423/fullglioblastomalactylationsubtypeprognosisinfiltration
spellingShingle Yanliang Tang
Xiaoli Zhang
Xiaofei Tang
Ye Yuan
Wenwen Wang
Lactylation-related gene signatures identify glioma molecular subtypes with prognostic, immunological, and therapeutic implications
Frontiers in Oncology
glioblastoma
lactylation
subtype
prognosis
infiltration
title Lactylation-related gene signatures identify glioma molecular subtypes with prognostic, immunological, and therapeutic implications
title_full Lactylation-related gene signatures identify glioma molecular subtypes with prognostic, immunological, and therapeutic implications
title_fullStr Lactylation-related gene signatures identify glioma molecular subtypes with prognostic, immunological, and therapeutic implications
title_full_unstemmed Lactylation-related gene signatures identify glioma molecular subtypes with prognostic, immunological, and therapeutic implications
title_short Lactylation-related gene signatures identify glioma molecular subtypes with prognostic, immunological, and therapeutic implications
title_sort lactylation related gene signatures identify glioma molecular subtypes with prognostic immunological and therapeutic implications
topic glioblastoma
lactylation
subtype
prognosis
infiltration
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1613423/full
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AT xiaolizhang lactylationrelatedgenesignaturesidentifygliomamolecularsubtypeswithprognosticimmunologicalandtherapeuticimplications
AT xiaofeitang lactylationrelatedgenesignaturesidentifygliomamolecularsubtypeswithprognosticimmunologicalandtherapeuticimplications
AT yeyuan lactylationrelatedgenesignaturesidentifygliomamolecularsubtypeswithprognosticimmunologicalandtherapeuticimplications
AT wenwenwang lactylationrelatedgenesignaturesidentifygliomamolecularsubtypeswithprognosticimmunologicalandtherapeuticimplications