Overexpression of Epithelial Splicing Regulatory Protein 1 in Metastatic Lesions of Serous Ovarian Carcinoma Correlates with Poor Patient Prognosis.

Cancer biotherapy & radiopharmaceuticals Pub Date : 2022-11-01 Epub Date: 2021-09-08 DOI:10.1089/cbr.2021.0215
Xinxin Lu, Runzhou Li, Xingshuang Wang, Qixuan Guo, Ling Wang, Xin Zhou
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引用次数: 2

Abstract

Background: Epithelial splicing regulatory proteins (ESRPs) can regulate alternative splicing of RNA and play roles in tumorigenesis and development of various malignancies. In this study, bioinformatic analyses and immunohistochemistry (IHC) were used to investigate the function of ESPRs in serous ovarian carcinoma (SOC) oncogenesis and metastasis. Materials and Methods: The mRNA levels of ESRPs were analyzed by Oncomine and gene expression profiling interactive analysis (GEPIA). Prognostic values of ESRPs were analyzed by GEPIA and the UALCAN website. Genetic variations of ESRPs were analyzed by cBioPortal. ESRP1 was selected for further research. The relationship between ESRP1 and immunoregulatory molecules was studied by using the TISIDB database. ESRP1 protein expression in OC was investigated via IHC assays. Results: ESRP1 and ESRP2 mRNA were significantly upregulated in SOC (p < 0.05). The prognostic value of ESRP1 mRNA in SOC was inconsistent, and ESRP2 mRNA level did not relate to prognosis for OC patients. The IHC results showed higher ESRP1 expression in OC tissues than in normal ovarian tissues (p = 0.002), and ESRP1 expression in metastatic lesions of OC patients was higher than in paired primary OC tissues (p = 0.035). The ESRP1 expression was related to FIGO stage, differentiation, and peritoneal metastasis (p = 0.016; 0.031; 0.038, respectively). The ESRP1 switch (the differential expression of ESRP1 between metastatic and primary tumor of ovarian carcinoma) was significantly associated with E-cadherin expression in metastatic OC tumors (p = 0.012). The ESRP1 expression in both metastasis and ESRP1 switch significantly correlated with poor prognosis of OC patients (p = 0.045; 0.038, respectively), and ESRP1 switch and FIGO stage were independent risk factors for OC patient prognosis (p = 0.033; 0.009, respectively). Conclusions: The ESRP1 may promote OC metastasis by promoting OC cell colonization via the mesenchymal-epithelial transition (MET) process. The ESRP1 expression in metastatic lesions of OC patients may be a biomarker for predicting prognosis and a potential therapeutic target in OC.
浆液性卵巢癌转移灶中上皮剪接调节蛋白1的过表达与不良预后相关
背景:上皮剪接调节蛋白(Epithelial splicing regulatory protein, esrp)可以调节RNA的选择性剪接,并在各种恶性肿瘤的发生和发展中发挥作用。本研究采用生物信息学分析和免疫组化(IHC)方法探讨espr在浆液性卵巢癌(SOC)发生转移中的作用。材料与方法:采用Oncomine和基因表达谱交互分析(GEPIA)分析esrp mRNA水平。通过GEPIA和UALCAN网站分析esrp的预后价值。利用基因门户分析esrp的遗传变异。选择ESRP1进行进一步研究。利用TISIDB数据库研究ESRP1与免疫调节分子的关系。通过免疫组化法研究ESRP1蛋白在OC中的表达。结果:ESRP1和ESRP2 mRNA在SOC中表达显著上调(p = 0.002),且ESRP1在OC患者转移灶中的表达高于配对原发OC组织(p = 0.035)。ESRP1表达与FIGO分期、分化及腹膜转移有关(p = 0.016;0.031;分别为0.038)。ESRP1开关(ESRP1在卵巢癌转移瘤和原发瘤之间的差异表达)与转移性OC肿瘤中E-cadherin的表达显著相关(p = 0.012)。转移灶及ESRP1开关中ESRP1表达与OC患者预后不良相关(p = 0.045;0.038), ESRP1开关和FIGO分期是OC患者预后的独立危险因素(p = 0.033;分别为0.009)。结论:ESRP1可能通过间充质-上皮转化(MET)过程促进OC细胞定植,从而促进OC转移。ESRP1在OC患者转移灶中的表达可能是预测OC预后的生物标志物和潜在的治疗靶点。
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