Qi Yuwen, Gao Yang, Cai Hongbing
Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, 169 Donghu Rd., Wuhan, Hubei, China.
Hubei Key Laboratory of Tumor Biological Behavior, Wuhan, China.
Discov Oncol. 2025 Jul 1;16(1):1249. doi: 10.1007/s12672-025-03043-8.
Ovarian clear cell cancer (OCCC) is a pathological type of ovarian cancer. OCCC responds poorly to platinum-based chemotherapy drugs and immunotherapy. Currently, there is a lack of targeted drugs for OCCC. It is very urgent to find new therapeutic targets for OCCC.
We used data from the eQTLGen consortium and deCODE, combined with large Genome-Wide Association Study (GWAS) cohort data, to perform drug target Mendelian randomization (MR) analysis. Colocalization analysis was used to identify target genes. Then, we analyzed single-cell sequencing data from the GEO database, combing with gene enrichment analysis to explore possible molecular mechanisms. Drug screening and molecular docking verified the medicinal value of the targets.
Three genes were selected in the MR analysis. Colocalization supported two of them, PPP1R14A and PTGS2. Single-cell sequencing analysis showed that these genes were related to tumor immunity. Drug prediction and molecular docking showed that PTGS2 had druggable potential.
This study identified two potential drug targets for OCCC. These drug targets may be relevant to tumor immunotherapy. However, further studies are necessary to confirm these findings and clarify the underlying mechanisms.
卵巢透明细胞癌（OCCC）是卵巢癌的一种病理类型。OCCC对铂类化疗药物和免疫疗法反应不佳。目前，OCCC缺乏靶向药物。寻找OCCC的新治疗靶点非常迫切。
我们使用了来自eQTLGen联盟和deCODE的数据，结合大型全基因组关联研究（GWAS）队列数据，进行药物靶点孟德尔随机化（MR）分析。共定位分析用于鉴定靶基因。然后，我们分析了来自GEO数据库的单细胞测序数据，并结合基因富集分析来探索可能的分子机制。药物筛选和分子对接验证了靶点的药用价值。
在MR分析中选择了三个基因。共定位支持其中两个基因，即PPP1R14A和PTGS2。单细胞测序分析表明这些基因与肿瘤免疫相关。药物预测和分子对接表明PTGS2具有成药潜力。
本研究确定了OCCC的两个潜在药物靶点。这些药物靶点可能与肿瘤免疫治疗有关。然而，需要进一步研究来证实这些发现并阐明潜在机制。
