Background: GALNT2, a key enzyme that initiates mucin-type O-glycosylation, plays a critical role in the malignant transformation and progression of tumors. However, their pan-cancer expression patterns, prognostic significance, and biological functions remain poorly understood. This study aimed to comprehensively investigate the role of GALNT2 in cancer using multidatabase integration. Methods: We analyzed GALNT2 expression, clinical relevance, genetic alterations, and functional states across 33 cancer types using public databases, including the Cancer Genome Atlas, Genotype-Tissue Expression project, Human Protein Atlas, cBioPortal for Cancer Genomics, Gene Expression Profiling Interactive Analysis 2, Tumor-Immune System Interaction Database, Kaplan–Meier plotter, Cancer Single-Cell State Atlas, and Gene Set Cancer Analysis Lite. Protein–protein interaction networks were constructed using Cytoscape, and functional enrichment was assessed using gene set enrichment analysis. Results: GALNT2 was significantly overexpressed in bladder urothelial carcinoma, breast invasive carcinoma, colon adenocarcinoma, head and neck squamous cell carcinoma, kidney chromophobe, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, lung adenocarcinoma, and lung squamous cell carcinoma. Moreover, high GALNT2 expression correlated with advanced cancer stage and metastasis, whereas low GALNT2 expression was associated with increased overall survival in kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, and lung adenocarcinoma. Receiver operating characteristic analysis revealed a high diagnostic value (area under the curve > 0.8) for 13 cancers, including esophageal squamous cell carcinoma, sarcoma, and skin cutaneous melanoma. GALNT2 interacts with core-1 β1,3-galactosyltransferase and glucosaminyl (N-acetyl) transferase 1 to modulate cancer-related pathways and immune regulation. The results of this study suggest that GALNT2 can be used as a diagnostic, prognostic, and immunological indicator in a spectrum of cancers. Conclusions: GALNT2 exhibits diverse expression, prognostic, and diagnostic profiles across cancer types. Our findings demonstrated that GALNT2 regulates key signaling pathways via glycosylation and interacts with critical genes, highlighting its potential as a biomarker and therapeutic target in pancreatic cancer.
Lin et al. (Wed,) studied this question.
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