Lu Xue-An, Pan Yan-Nan, Xie Chen-Jun, Wang Qing-Wen, Xu Shi-Wei, Wang Qin, He Youzhao, Wang Lei-Sheng, Mao Yong, Hu Hao
Donghai County People's Hospital, Lianyungang, Jiangsu, China.
Wuxi Medical College, Jiangnan University, Wuxi, 214122, China.
Clin Transl Oncol. 2025 Jun 25. doi: 10.1007/s12094-025-03976-0.
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.
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.
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.
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.
本研究旨在探讨尿苷二磷酸葡萄糖醛酸基转移酶1家族多肽A6（UGT1A6）在胰腺癌中的作用，重点关注其表达模式、临床意义、对肿瘤进展的影响以及在免疫逃逸中的潜在作用。
使用TNMplot、GEPIA和癌症基因组图谱（TCGA）数据库分析多种癌症类型中UGT1A6的表达。对胰腺癌细胞系进行功能实验，包括蛋白质印迹法、qRT-PCR、CCK-8和Transwell实验，以评估其增殖和迁移能力。利用CellChat进行单细胞数据和细胞间通讯分析，以研究UGT1A6对免疫微环境的影响。
UGT1A6在胰腺癌组织中的表达显著上调，且与总体生存率低（P = 0.0095）、TNM分期晚期以及KRAS和TP53突变相关。功能实验表明，敲低UGT1A6可显著抑制胰腺癌细胞的增殖和迁移。免疫分析显示UGT1A6与免疫抑制分子（CD274、PDCD1LG2、HAVCR2和TGFBR1）以及特定免疫细胞浸润模式呈正相关，表明其在促进免疫逃逸中可能发挥作用。单细胞分析进一步显示，表达UGT1A6的肿瘤上皮细胞与免疫细胞之间的通讯增强，这可能会损害抗肿瘤免疫反应。
UGT1A6是胰腺癌进展和免疫逃逸的关键驱动因素，正成为一种有前景的预后生物标志物和治疗靶点。未来的研究应侧重于阐明详细的分子机制，并在精准治疗中验证其临床应用价值。
