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Abstract
Aim: This study explored the prognostic value of N-glycan biosynthesis (NGB) in lower-grade glioma (LGG) and aimed to develop a machine learning model for enhanced prognostic accuracy.
Method: LGG patient transcriptome data were analyzed to identify NGB-related genes. Consensus clustering identified subgroups based on NGB expression. A prognostic NGB signature (pNGB) was developed using machine learning. The pNGB score's association with cell proliferation, inflammation, treatment response, tumor recurrence, and the immune microenvironment was also explored.
Results: A 22-gene pNGB signature was identified, with MGAT1 and TUSC3 having the highest and lowest hazard ratios, respectively. Two distinct clusters (C1 and C2) with differential pNGB expression and survival outcomes were revealed. NGB pathway analysis indicated an overall poor prognosis, except for MGAT4C and TUSC3. The Enet-based survival model showed superior discriminatory power and reliability. The NGB risk score correlated with increased cell proliferation, inflammation, and altered immune landscape. Additionally, the score is linked to treatment response and tumor recurrence.
Conclusion: This study highlights the critical role of NGB in LGG progression and proposes a pNGB-based model for prognosis. The NGB risk score shows promise as a prognostic biomarker and potential therapeutic target in LGG.
Keywords
Low-grade glioma
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N-glycan biosynthesis
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machine learning
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metabolic dysfunction
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tumor recurrence
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Yihao Zhu, Liangyuan Geng, Fuduo Bo, Yang Xu, Jindou Wei, Yansong Zhang, Chunfa Qian.
Machine learning-based integration of omics and clinical data reveals an N-glycan biosynthesis signature predictive of the outcome in low-grade glioma: an in silico study.
Journal of Cancer Metastasis and Treatment, 2024, 10: 23 DOI:10.20517/2394-4722.2024.32
| [1] |
Teng C,Li Y.Recurrence- and malignant progression-associated biomarkers in low-grade gliomas and their roles in immunotherapy.Front Immunol2022;13:899710 PMCID:PMC9168984
|
| [2] |
Fukuya Y,Maruyama T.Tumor recurrence patterns after surgical resection of intracranial low-grade gliomas.J Neurooncol2019;144:519-28
|
| [3] |
Shaw EG,Coons SW.Recurrence following neurosurgeon-determined gross-total resection of adult supratentorial low-grade glioma: results of a prospective clinical trial.J Neurosurg2008;109:835-41 PMCID:PMC3833272
|
| [4] |
Sanai N,Berger MS.Low-grade gliomas in adults.J Neurosurg2011;115:948-65
|
| [5] |
Murphy ES,Parsons M.Risk factors for malignant transformation of low-grade glioma.Int J Radiat Oncol Biol Phys2018;100:965-71
|
| [6] |
Westphal M.The neurobiology of gliomas: from cell biology to the development of therapeutic approaches.Nat Rev Neurosci2011;12:495-508
|
| [7] |
Jansen E,Ruess D.Observation after surgery for low grade glioma: long-term outcome in the light of the 2016 WHO classification.J Neurooncol2019;145:501-7
|
| [8] |
Poff A,Egan KM,D’Agostino D.Targeting the warburg effect for cancer treatment: ketogenic diets for management of glioma.Semin Cancer Biol2019;56:135-48 PMCID:PMC6927557
|
| [9] |
Claus EB,Wiencke JK.Survival and low-grade glioma: the emergence of genetic information.Neurosurg Focus2015;38:E6 PMCID:PMC4361022
|
| [10] |
Tran TO,Lam LHT.ALDH2 as a potential stem cell-related biomarker in lung adenocarcinoma: comprehensive multi-omics analysis.Comput Struct Biotechnol J2023;21:1921-9 PMCID:PMC10018390
|
| [11] |
Dang HH,Nguyen TTT.Identifying GPSM family members as potential biomarkers in breast cancer: a comprehensive bioinformatics analysis.Biomedicines2021;9:1144 PMCID:PMC8471503
|
| [12] |
Taniguchi N.Glycans and cancer: role of N-glycans in cancer biomarker, progression and metastasis, and therapeutics.Adv Cancer Res2015;126:11-51
|
| [13] |
Pinho SS.Glycosylation in cancer: mechanisms and clinical implications.Nat Rev Cancer2015;15:540-55
|
| [14] |
Medina-Cano D,Nguyen LS.High N-glycan multiplicity is critical for neuronal adhesion and sensitizes the developing cerebellum to N-glycosylation defect.Elife2018;7:e38309 PMCID:PMC6185108
|
| [15] |
Xu Q,Qu C.Chitosan oligosaccharides inhibit epithelial cell migration through blockade of N-acetylglucosaminyltransferase V and branched GlcNAc structure.Carbohydr Polym2017;170:241-6
|
| [16] |
Cui Y,Zhang P.B4GALT1 promotes immune escape by regulating the expression of PD-L1 at multiple levels in lung adenocarcinoma.J Exp Clin Cancer Res2023;42:146 PMCID:PMC10259029
|
| [17] |
Colaprico A,Olsen C.TCGAbiolinks: an R/Bioconductor package for integrative analysis of TCGA data.Nucleic Acids Res2016;44:e71 PMCID:PMC4856967
|
| [18] |
Durinck S,Birney E.Mapping identifiers for the integration of genomic datasets with the R/Bioconductor package biomaRt.Nat Protoc2009;4:1184-91 PMCID:PMC3159387
|
| [19] |
Hänzelmann S,Guinney J.GSVA: gene set variation analysis for microarray and RNA-seq data.BMC Bioinformatics2013;14:7 PMCID:PMC3618321
|
| [20] |
Aran D,Butte AJ.xCell: digitally portraying the tissue cellular heterogeneity landscape.Genome Biol2017;18:220 PMCID:PMC5688663
|
| [21] |
Wilkerson MD.ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking.Bioinformatics2010;26:1572-3 PMCID:PMC2881355
|
| [22] |
Ritchie ME,Wu D.Limma powers differential expression analyses for RNA-sequencing and microarray studies.Nucleic Acids Res2015;43:e47 PMCID:PMC4402510
|
| [23] |
Liu Z,Weng S.Machine learning-based integration develops an immune-derived lncRNA signature for improving outcomes in colorectal cancer.Nat Commun2022;13:816 PMCID:PMC8831564
|
| [24] |
Lin Y.The role of N-glycosylation in cancer.Acta Pharm Sin B2024;14:1098-110 PMCID:PMC10935144
|
| [25] |
Li Y,Zhu H.N-acetylglucosaminyltransferase I promotes glioma cell proliferation and migration through increasing the stability of the glucose transporter GLUT1.FEBS Lett2020;594:358-66
|
| [26] |
Wu Q,Macaulay RJ.Epigenetic activation of TUSC3 sensitizes glioblastoma to temozolomide independent of MGMT promoter methylation status.Int J Mol Sci2023;24:15179 PMCID:PMC10606804
|
| [27] |
Liang Q,Wang B.HCMV-encoded miR-UL112-3p promotes glioblastoma progression via tumour suppressor candidate 3.Sci Rep2017;7:44705 PMCID:PMC5356197
|
| [28] |
Chang X,Zhao R.DDOST correlated with malignancies and immune microenvironment in gliomas.Front Immunol2022;13:917014 PMCID:PMC9260604
|
| [29] |
Qi Y,Liu X.Comprehensive analysis identified glycosyltransferase signature to predict glioma prognosis and TAM phenotype.Biomed Res Int2023;2023:6082635 PMCID:PMC9859707
|
| [30] |
Liu P,Liu Z.Inhibition of ALG3 stimulates cancer cell immunogenic ferroptosis to potentiate immunotherapy.Cell Mol Life Sci2022;79:352 PMCID:PMC11072400
|
| [31] |
Lin W,Zhang H.Identification of molecular subtypes based on inflammatory response in lower-grade glioma.Inflamm Regen2022;42:29 PMCID:PMC9526248
|
| [32] |
Han T,Qu M,Li Q.Comprehensive analysis of inflammatory response-related genes, and prognosis and immune infiltration in patients with low-grade glioma.Front Pharmacol2021;12:748993 PMCID:PMC8545815
|
| [33] |
Geng F,Yuan YF.The expression of core fucosylated E-cadherin in cancer cells and lung cancer patients: prognostic implications.Cell Res2004;14:423-33
|
| [34] |
Isaji T,Kameyama A,Fukuda T.A complex between phosphatidylinositol 4-kinase IIα and integrin α3β1 is required for N-glycan sialylation in cancer cells.J Biol Chem2019;294:4425-36 PMCID:PMC6433072
|
| [35] |
Li R,Yang X,Liu P.Crosstalk between dendritic cells and regulatory T cells: protective effect and therapeutic potential in multiple sclerosis.Front Immunol2022;13:970508 PMCID:PMC9513370
|
| [36] |
Wang G,Wang Z.Tumor-associated microglia and macrophages in glioblastoma: from basic insights to therapeutic opportunities.Front Immunol2022;13:964898 PMCID:PMC9363573
|