He Shiqing,Wang Meide,Sha Yongliang.Construction and validation of a prognostic model for neuroblastoma based upon glycosyltransferase genes[J].Journal of Clinical Pediatric Surgery,,():333-343.[doi:10.3760/cma.j.cn101785-20260124-00038]
Construction and validation of a prognostic model for neuroblastoma based upon glycosyltransferase genes
- Keywords:
- Neuroblastoma; Glycosyltransferases; Prognosis; Models; Statistical; Risk Assessment
- Abstract:
- Objective To construct and validate a prognosis model for neuroblastoma (NB) based on glycosyltransferases (GTs).Methods GEO85047 from the Gene Expression Omnibus (GEO) database was used as training set while the TARGET database as validation set.Based upon 213 GTGs reported in the literature,single/multi-factor Cox regression analysis,protein-protein interaction (PPI) and least absolute shrinkage and selection operator (LASSO) regression were employed for screening prognostic-related GTs and constructing a prognosis model.The risk score was calculated.They were assigned into low-risk and high-risk groups based upon median value.Kaplan-Meier curve,ROC curve and Cox regression were utilized for observing the stability and prognostic efficacy of the model.Univariate and multivariate Cox regression analyses were used for evaluating the correlation between the model,other clinical factors and tumor prognosis.Functional enrichment analysis of differentially expressed genes between high-risk and low-risk groups was performed.Single sample gene set enrichment analysis (ssGSEA) was used for examining the relationship between the model and immune cell infiltration.A total of 81 NB and 25 ganglioneuroblastoma tumor tissue specimens were selected for immunohistochemical detection of B3GALT4 expression.And 9464D and 975A2 in NB cell lines were divided into Scramble group (transfection with B3GALT4 knockdown lentiviral vector),Sh-B3GALT4 group (transfection with B3GALT4 knockdown lentiviral vector),Vector group (transfection with B3GALT4 overexpression lentiviral vector) and OE-B3GALT4 group (B3GALT4 overexpression lentiviral vector).Western blot,quantitative real-time polymerase chain reaction (qRT-PCR),CCK-8,clone formation and Transwell assay were employed for detecting cell proliferation,invasion and migratory capabilities.Results A prognosis model consisting of PIGZ,GALNT7,GALNT2,GALNT14,EXTL2,DPY19L3,CHPF2,B3GNT5,B3GALT4 and ALG3 genes was constructed.Survival analysis revealed that high-risk group had significantly worse prognosis than low-risk group (P<0.01).The AUC of the prognostic model for 1/3/5-year survival rate was 0.807,0.825 and 0.837 (training set); 0.654,0.675 and 0.662 (validation set).Univariate and multivariate Cox regression analysis indicated that age,stage and the prognosis model were independent risk factors for prognosis.The high-risk group became enriched predominantly in pathways such as protein targeting endoplasmic reticulum,cell membrane and mRNA degradation processes of nuclear transcription.The number of CD4+ T cells and CD8+ T cells infiltrating in high-risk group was higher than that in low-risk group (P<0.05).B3GALT4 was lowly expressed in NB tissues.Down-regulation of B3GALT4 could promote the proliferation,invasion and migratory capabilities of NB cells.Conclusions The NB prognosis model constructed based upon glycosyltransferase genes may predict the prognosis of children and immune microenvironment.Up-regulation of B3GALT4 arrests the malignant phenotype of NB.It is expected to become a new molecular marker for NB.
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Memo
收稿日期:2026-1-24。
基金项目:江苏省卫生健康委科研项目(Z2024033);徐州医科大学附属医院发展基金资助项目(XYFM202407);徐州市卫生健康委科技项目(XWKYHT20250021);徐州医科大学附属医院发展基金资助项目(XYFM202335)
通讯作者:沙永亮,Email:sylv4_2012@sina.com