Li Zhengwen, Wang Yue, Yang Kaichuan, Li Chujie, Zhang Ming
School of Pharmacy, Chengdu University, 2025 Chengluo Avenue, Chengdu 610106, China.
Cell Biology-Inspired Tissue Engineering, Institute for Technology-Inspired, Regenerative Medicine, Maastricht University, 6200 MD Maastricht, The Netherlands.
Genes (Basel). 2025 Apr 13;16(4):449. doi: 10.3390/genes16040449.
Quercetin, a dietary flavonoid and a widely used supplement, has hepatoprotective properties. Given its urate-lowering effects and epidemiological evidence linking elevated serum urate levels to liver cancer risk, we tested whether quercetin reduces liver cancer risk via modulation of urate levels by bioinformatics methods.
We employed drug-target Mendelian randomization using genome-wide association study summary statistics from public databases (e.g., MRC-IEU) to assess genetic associations, and integrated these findings with GEO datasets (such as GSE138709 and GSE179443) and immune infiltration analyses using tools like xCell, TIMER.
Our analyses identified -mediated urate elevation as a causal risk factor for hepatocellular carcinoma (OR = 1.001, < 0.01), cholangiocarcinoma (OR = 3.424, < 0.01), and liver fibrosis (OR = 2.528, < 0.01). Single-cell transcriptomics revealed elevated expression in cholangiocarcinoma endothelial cells, while immune infiltration analysis showed significant associations between expression and both endothelial cell and macrophage infiltration. Survival analysis further indicated that was not associated with poor prognosis in cholangiocarcinoma or hepatocellular carcinoma.
Considering quercetin's multifaceted interactions with BCRP/, our findings support its potential use as a preventive dietary supplement for hepatic diseases rather than as an adjunctive therapy for established liver cancer.
槲皮素是一种膳食类黄酮，也是一种广泛使用的补充剂，具有肝脏保护特性。鉴于其降低尿酸的作用以及血清尿酸水平升高与肝癌风险相关的流行病学证据，我们通过生物信息学方法测试了槲皮素是否通过调节尿酸水平来降低肝癌风险。
我们利用来自公共数据库（如MRC - IEU）的全基因组关联研究汇总统计数据进行药物靶点孟德尔随机化，以评估基因关联，并将这些结果与GEO数据集（如GSE138709和GSE179443）以及使用xCell、TIMER等工具进行的免疫浸润分析相结合。
我们的分析确定介导的尿酸升高是肝细胞癌（OR = 1.001，<0.01）、胆管癌（OR = 3.424，<0.01）和肝纤维化（OR = 2.528，<0.01）的因果风险因素。单细胞转录组学显示胆管癌内皮细胞中表达升高，而免疫浸润分析表明表达与内皮细胞和巨噬细胞浸润均存在显著关联。生存分析进一步表明在胆管癌或肝细胞癌中与不良预后无关。
考虑到槲皮素与BCRP/的多方面相互作用，我们的研究结果支持其作为肝脏疾病预防性膳食补充剂的潜在用途，而非作为已确诊肝癌的辅助治疗方法。
