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

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.