UGT1A6 in pancreatic cancer: a promising prognostic biomarker and therapeutic target.

Objective: This study aimed to explore the role of the UDP glucuronosyltransferase 1 family, polypeptide A6 (UGT1A6), in pancreatic cancer, focusing on its expression patterns, clinical significance, impact on tumor progression, and potential involvement in immune evasion.

Methods: UGT1A6 expression across multiple cancer types was analyzed using TNMplot, GEPIA, and The Cancer Genome Atlas (TCGA) databases. Functional experiments, including western blotting, qRT-PCR, CCK-8, and Transwell assays, were performed on pancreatic cancer cell lines to assess their proliferation and migration capabilities. Single-cell data and cell-cell communication analyses using CellChat were conducted to investigate UGT1A6's influence on the immune microenvironment.

Results: UGT1A6 expression was significantly upregulated in pancreatic cancer tissues and correlated with poor overall survival (P = 0.0095), advanced TNM stage, and KRAS and TP53 mutations. Functional experiments revealed that UGT1A6 knockdown markedly suppressed the proliferation and migration of pancreatic cancer cells. Immune analysis demonstrated a positive correlation between UGT1A6 and immunosuppressive molecules (CD274, PDCD1LG2, HAVCR2, and TGFBR1) and specific immune cell infiltration patterns, indicating a potential role in promoting immune evasion. Single-cell analysis further showed enhanced communication between UGT1A6-expressing tumor epithelial cells and immune cells, which might impair antitumor immune responses.

Conclusion: UGT1A6 acts as a key driver of pancreatic cancer progression and immune evasion, and is emerging as a promising prognostic biomarker and therapeutic target. Future studies should focus on clarifying the detailed molecular mechanisms and validating their clinical utility in precision therapy.