Wang Juan, Sun Ji, Liang Chen, Ou Haibin, Liu Jiong, Ye Aoqing, Wu Qiuji, Liu Yu
Esophagus, Mediastinum and Lymphatic Oncology Department, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
Discov Oncol. 2025 Aug 25;16(1):1621. doi: 10.1007/s12672-025-02777-9.
Esophageal carcinoma (EC) is the eighth most common cancer, which is a major health problem on a global scale. Comprehensive treatments such as surgery, radiotherapy and chemotherapy have demonstrated efficacy in certain patients with early-stage esophageal carcinoma. However, it is crucial to explore improved treatment modalities for individuals with advanced, recurrent and metastatic esophageal carcinoma.
The eQTL datasets were obtained from Drug-Gene Interaction Database (DGIdb V.4.2.0) and an interesting review about druggable genes. The two-sample MR was used to identify potential drug targets. Co-localization analysis was applied to evaluate if the genes expression single nucleotide polymorphisms (SNPs) drove and was associated with EC risk. And drug prediction and molecular docking were used to verify the pharmaceutical value of potential clinical drugs.
The present study found thirty potential drug targets that were remarkably correlated with the risk of developing esophageal carcinoma at least in two eQTL datasets by two-sample MR analysis. Five genes colocalized with esophageal carcinoma were identified through colocalization analysis and the medicinal value of four potential clinical drugs was testified by molecular docking.
We identified five drug targets by MR analysis and co-localization analysis and four drugs by drug prediction and molecular docking analysis respectively, which provide new insights for treatment of esophageal carcinoma.
食管癌（EC）是第八大常见癌症，是全球范围内的一个主要健康问题。手术、放疗和化疗等综合治疗已在某些早期食管癌患者中显示出疗效。然而，探索针对晚期、复发和转移性食管癌患者的改进治疗方式至关重要。
从药物-基因相互作用数据库（DGIdb V.4.2.0）和一篇关于可成药基因的有趣综述中获取eQTL数据集。采用两样本孟德尔随机化（MR）来识别潜在的药物靶点。应用共定位分析来评估基因表达单核苷酸多态性（SNP）是否驱动并与食管癌风险相关。并使用药物预测和分子对接来验证潜在临床药物的药学价值。
本研究通过两样本MR分析发现了30个潜在的药物靶点，这些靶点至少在两个eQTL数据集中与食管癌发生风险显著相关。通过共定位分析确定了5个与食管癌共定位的基因，并通过分子对接证实了4种潜在临床药物的药用价值。
我们分别通过MR分析和共定位分析确定了5个药物靶点，通过药物预测和分子对接分析确定了4种药物，这为食管癌的治疗提供了新的见解。
