| Objective:In order to discuss the feasibility and significance of EXO1 targeting therapy in EOC,the correlation between the expression level of EXO1 and clinical feature/prognosis of EOC was analyzed by analyzing and detecting the transcription and expression level of EXO1 in epithelial ovarian cancer(EOC)tissue.Methods:(1)Bioinformatics method was employed to analyze the difference of EXO1 mRNA level between normal ovary tissue and EOC tissue,and the relationship between its transcriptional level and EOC prognosis was evaluated.(2)Fresh frozen specimens of EOC patients were collected,who were diagnosed and treated in the Second Hospital of Jilin University from February 2018 to August 2019.Western blot was performed to detect the expression level of EXO1 protein in both EOC tissue and EOC adjacent tissue.(3)Paraffin-embedded Specimens of EOC patients were collected for retrospective analysis,who were diagnosed and treated in the Second Hospital of Jilin University from May 2012 to May 2019.Immunohistochemical staining of these EOC specimens was used to evaluate the expression level of EXO1 protein in EOC tissue.The correlation between EXO1 expression and clinical features in EOC was analyzed,including ages,preoperative CA125 and HE4 levels,pathological stages,tumor size,EOC types,pathological grades,ascites volume and lymph nodes metastasis.KaplanMeier analysis was utilized to analyze the relationship between EXO1 expression/clinical features and overall survival of EOC patients.Finally,COX regression analysis was utilized to find out the independent risk factors of EOC overall survival.Results:(1)Bioinformatics analysis with Oncomine database showed the transcription level of EXO1 in serous,mucinous,endometrioid and clear cell carcinoma tissue is obviously higher than normal ovary tissue(P<0.01).Bioinformatics analysis with Kaplan-Meier database showed that among EOC patients with early stage,low grade or TP53 mutation,the prognosis of patients with high level of EXO1 mRNA is poorer than those with low level of EXO1 mRNA(P<0.05).(2)Western blot results showed that compared with EOC adjacent tissue,EXO1 protein level is significantly up-regulated in EOC tissue(P<0.01).(3)Results of immunohistochemical staining showed that the expression level of EXO1 protein is closely associated with ages of EOC patients.High expression rate of EOC patients <53 years old is apparently higher than patients ≥53 years old(P<0.05).(4)EOC prognosis is significantly associated with pathological stages,EOC types,pathological grades and the expression level of EXO1 in EOC tissue(P<0.05).Compared to EOC patients with early stage,type I,low grade or low expression level of EXO1,overall survival of EOC patients who are advanced stage,type II,high grade or with high expression level of EXO1 is obviously shorter.(5)Both advanced stage(stage III+IV)and high expression level of EXO1 are independent risk factors of overall survival in EOC(p<0.01).More specifically,the risk of death in advanced stage EOC patients is 8.237 times more than patients who are early stage.The risk of death in EOC patients with high expression level of EXO1 is 4.861 times more than the patients with low expression level of EXO1.Conclusions:(1)Compared with normal ovary tissue,the transcription level of EXO1 is higher in serous,mucinous,endometrioid and clear cell carcinoma tissue.Among EOC patients who are early stage,low grade or with TP53 mutation,patients with high EXO1 mRNA level have poorer prognosis.(2)Compared with EOC adjacent tissue,the expression level of EXO1 protein is significantly higher in EOC tissue.(3)The high expression rate of EXO1 in EOC patients aged <53 years was higher than that in patients aged ≥53 years.(4)Pathological stages,EOC types,pathological grades and the expression level of EXO1 are closely related to overall survival of EOC.Among them,both advanced stage(stage III+IV)and high expression of EXO1 are the independent risk factors of overall survival in EOC. |
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