Background. Pancreatic cancer (PC) is one of the most common cancers worldwide, with high mortality. The UGT1A gene family plays important roles in pharmacology and toxicology, contributing to interindividual differences in drug disposition. However, mRNA expression and prognostic value of the UGT1A gene family in PC have not been identified. Methods. Oncomine, GEPIA2, DAVID 6.8, Metascape, Kaplan-Meier plotter, cBioPortal, GeneMANIA, TRRUST v2, TIMER, and R software were used in our study. Results. The transcriptional levels of UGT1A1/3/6/8/9/10 in PC tissues were significantly higher than those in normal tissues. These results were further validated using five pairs of PC tumor tissues and adjacent nontumor tissues. A significant correlation was found between the expression of UGT1A1/6/10 and the pathological stage of PC. PC patients with lower transcriptional levels of UGT1A1/4/5/6/10 were associated with a better prognosis. The differentially expressed UGT1A gene family functions were primarily related to the glucuronidation pathway, cytokine-cytokine receptor interactions, and the ILK signaling pathway. Our data suggest that HNF1A, AHR, and CDX2 are key transcription factors for the UGT1A gene family. Furthermore, the expression levels of UGT1A1/3/8/9/10 were positively correlated with the activities of tumor-infiltrating immune cells, especially B cells. The expression levels of UGT1A6/9 were negatively correlated with macrophage infiltration levels. Conclusions. These results suggest that the UGT1A gene family could serve as a potential prognostic biomarker and target for PC. However, future studies are required to validate our findings and promote the clinical utility of the UGT1A gene family in PC.

中文翻译：

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UGT1A 基因家族成员可作为胰腺癌的潜在靶标和预后生物标志物

背景。胰腺癌（PC）是全球最常见的癌症之一，死亡率很高。UGT1A 基因家族在药理学和毒理学中发挥重要作用，导致药物处置的个体间差异。然而，尚未确定 PC 中 UGT1A 基因家族的 mRNA 表达和预后价值。方法。我们的研究中使用了 Oncomine、GEPIA2、DAVID 6.8、Metascape、Kaplan-Meier 绘图仪、cBioPortal、GeneMANIA、TRRUST v2、TIMER 和 R 软件。结果. PC组织中UGT1A1/3/6/8/9/10的转录水平显着高于正常组织。使用五对 PC 肿瘤组织和相邻的非肿瘤组织进一步验证了这些结果。UGT1A1/6/10的表达与PC的病理分期存在显着相关性。UGT1A1/4/5/6/10 转录水平较低的 PC 患者预后较好。差异表达的UGT1A基因家族功能主要与葡萄糖醛酸化途径、细胞因子-细胞因子受体相互作用和ILK信号通路有关。我们的数据表明 HNF1A、AHR 和 CDX2 是 UGT1A 基因家族的关键转录因子。此外，UGT1A1/3/8/9/10的表达水平与肿瘤浸润免疫细胞的活性呈正相关，尤其是B细胞。UGT1A6/9的表达水平与巨噬细胞浸润水平呈负相关。结论。这些结果表明，UGT1A 基因家族可以作为 PC 的潜在预后生物标志物和靶标。然而，未来的研究需要验证我们的发现并促进 UGT1A 基因家族在 PC 中的临床应用。