Liu Jingfang, Wu Beier, Wan Shihan, Jin Yanlu, Yang Li, Wu Meijuan, Xing Jie, Zhang Jiejie, Chen Xin, Yu Aijun
Department of Gynecological Oncology, Hangzhou Institute of Medicine (HIM), Zhejiang Cancer Hospital, Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China.
Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, 310022, China.
J Ovarian Res. 2025 Apr 7;18(1):73. doi: 10.1186/s13048-025-01603-8.
Tricho-rhino-phalangeal syndrome-1 (TRPS1), an atypical GATA transcription factor, plays a critical role in diverse physiological and pathological processes and holds potential as a biomarker for diseases and targeted tumor therapies. This study explores TRPS1 expression in ovarian clear cell carcinoma (OCCC), its correlation with patient prognosis, and its involvement in OCCC pathogenesis.
To investigate TRPS1 expression, we analyzed ovarian tissues from 50 OCCC patients and 25 normal tissues (from patients with uterine leiomyoma) via immunohistochemistry. Statistical methods, including Chi-square tests, Kaplan-Meier survival analysis, and Cox regression, were employed to evaluate the correlation between TRPS1 expression and clinicopathological parameters. In OCCC cell lines (TOV21G and ES-2), TRPS1 expression was quantified using qRT-PCR and Western blot. Functional studies were conducted by silencing TRPS1 in TOV21G cells with small interfering RNA and inducing overexpression in ES-2 cells using a plasmid. Cellular proliferation and migration were assessed through CCK-8, colony formation, and Transwell assays. Finally, Western blot analysis was performed to investigate the link between TRPS1 and EMT-related molecular pathways.
TRPS1 protein expression was significantly higher in OCCC tissues compared to normal tissues and was positively associated with lymph node metastasis and advanced clinical stage. High TRPS1 expression was linked to shorter overall and recurrence-free survival in OCCC patients. In vitro, TRPS1 knockdown suppressed cell proliferation, migration, and invasion, accompanied by reduced levels of invasion-promoting proteins (N-cadherin, MMP2, MMP9) and increased expression of the invasion-inhibiting protein E-cadherin. Conversely, TRPS1 overexpression promoted the expression of invasion-promoting proteins.
TRPS1 is overexpressed in OCCC and is associated with poor prognosis, serving as an independent predictor of patient outcomes. Its elevated expression enhances OCCC cell proliferation, migration, and invasion by regulating proteins involved in the epithelial-to-mesenchymal transition (EMT) pathway. These findings highlight TRPS1 as a critical player in OCCC pathogenesis and a potential biomarker and therapeutic target for disease management.
毛发-鼻-指综合征1型(TRPS1)是一种非典型GATA转录因子,在多种生理和病理过程中起关键作用,有望成为疾病的生物标志物和肿瘤靶向治疗靶点。本研究探讨TRPS1在卵巢透明细胞癌(OCCC)中的表达、其与患者预后的相关性以及其在OCCC发病机制中的作用。
为研究TRPS1的表达,我们通过免疫组织化学分析了50例OCCC患者的卵巢组织和25例正常组织(来自子宫肌瘤患者)。采用卡方检验、Kaplan-Meier生存分析和Cox回归等统计方法评估TRPS1表达与临床病理参数之间的相关性。在OCCC细胞系(TOV21G和ES-2)中,使用qRT-PCR和蛋白质印迹法对TRPS1表达进行定量。通过用小干扰RNA沉默TOV21G细胞中的TRPS1并使用质粒诱导ES-2细胞中的过表达来进行功能研究。通过CCK-8、集落形成和Transwell实验评估细胞增殖和迁移。最后,进行蛋白质印迹分析以研究TRPS1与上皮-间质转化(EMT)相关分子途径之间的联系。
与正常组织相比,TRPS1蛋白在OCCC组织中的表达显著更高,并且与淋巴结转移和临床晚期呈正相关。TRPS1高表达与OCCC患者较短的总生存期和无复发生存期相关。在体外,TRPS1敲低抑制细胞增殖、迁移和侵袭,同时侵袭促进蛋白(N-钙黏蛋白、MMP2、MMP9)水平降低,侵袭抑制蛋白E-钙黏蛋白表达增加。相反,TRPS1过表达促进侵袭促进蛋白的表达。
TRPS1在OCCC中过表达且与不良预后相关,是患者预后的独立预测指标。其表达升高通过调节参与上皮-间质转化(EMT)途径的蛋白来增强OCCC细胞的增殖、迁移和侵袭。这些发现突出了TRPS1在OCCC发病机制中的关键作用,以及作为疾病管理的潜在生物标志物和治疗靶点的可能性。