B4GALNT1 promotes carcinogenesis by regulating epithelial-mesenchymal transition in hepatocellular carcinoma based on pan-cancer analysis

Background: β-1,4-N-Acetyl galactosaminyltransferase1 (B4GALNT1) has been reported to play important roles in tumor progression and metastasis. Herein, we investigate the oncogenic roles of B4GALNT1 for hepatocellular carcinoma (HCC) based on immune microenvironment.

Methods: The Cancer Genome Atlas database and Genotype-Tissue Expression, cBioportal, ImmuCellAI, TIMER2 and other databases were searched to analyze the expression and clinical applications of B4GALNT1 in liver cancer patients. Kaplan-Meier survival analysis, Cox regression analysis, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analysis were utilized. Moreover, western blot assay, immune histochemistry staining, Cell Counting Kit-8 (CCK-8) assay, invasion and migration assay were performed to evaluate the function of B4GALNT1 in HCC.

Results: B4GALNT1 is overexpressed in 14 tumors, and the mRNA expression levels of B4GALNT1 were remarkably elevated in most tumor types, including HCC. In addition, B4GALNT1 expression was an independent prognostic factor, and a low expression of B4GALNT1 showed a better overall survival and disease-specific recurrence-free survival in patients with HCC. Gene set variation analysis indicated that B4GALNT1 presented a positive correlation with the epithelial-mesenchymal transition (EMT) pathway in HCC. B4GALNT1 expression was closely associated with immune activation genes in the HCC microenvironment. Moreover, B4GALNT1 expression was higher in HCC tissue than that in surrounding tissues. B4GALNT1 promoted the expression of apoptosis-related or EMT-related proteins and then decreased the expression of Bcl-2 and Bcl-xl in HCC cells, suggesting that B4GALNT1 knockdown significantly inhibited the proliferation and invasion of HCC cells.

Conclusions: B4GALNT1 may promote HCC development through regulating the EMT pathway, which suggests that B4GALNT1 may serve as a promising predictive biomarker and a potential therapeutic target for HCC.