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IGFBP3 and UBE2C are associated with protein modification pathways and serve as prognostic markers in glioma
1Department of Cardiology and The Key Laboratory of Cardiovascular Disease of Wenzhou, The First Affiliated Hospital, Wenzhou Medical University, Zhejiang, China.
Background:
Glioma, the most prevalent malignant primary CNS tumor, features aggressive proliferation and poor prognosis. The prognostic value of core protein modification pathway genes remains unclear.
Methods:
Metascape enrichment identified hub genes in protein modification. IGFBP3 and UBE2C were assessed via Kaplan-Meier, multivariate Cox regression, time-dependent ROC and partial correlation. Promoter methylation (TCGA) and NRI/IDI (CGGA) were analyzed.
Results:
High IGFBP3 and UBE2C predicted inferior survival across all WHO-grade primary and recurrent gliomas (log-rank P < 0.001). External TCGA validation yielded higher HRs (IGFBP3: N = 697, HR = 3.08; UBE2C: N = 690, HR = 4.58). In CGGA multivariate analysis,adjusted for age, grade and IDH status, IGFBP3 (HR = 2.03) and UBE2C (HR = 2.13) remained independent factors. In the TCGA cohort, time-dependent ROC showed moderate-to-good performance: IGFBP3 AUCs = 0.789 (1y), 0.798 (3y), 0.699 (5y); UBE2C AUCs = 0.784 (1y), 0.838 (3y), 0.808 (5y). Positive co-expression in primary and recurrent gliomas persisted after adjusting for grade, IDH status and 1p/19q codeletion (partial r = 0.138, P = 0.001). Significance held after further adjustment for 1p/19q codeletion and histology (IGFBP3: HR = 1.85; UBE2C: HR = 2.20). NRI and IDI verified incremental predictive value over clinical baselines. UBE2C promoter methylation negatively correlated with expression and differed by IDH status, while IGFBP3 lacked such epigenetic associations.
Conclusion:
IGFBP3 and UBE2C are robust glioma prognostic biomarkers involved in protein modification pathways. Cross-cohort stability and distinct methylation patterns support their use as auxiliary prognostic markers, awaiting prospective validation.
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