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Expression of folate receptor 1 and mesothelin proteins in epithelial ovarian cancer and their clinical significance
oleh: LIANG Zhen, DONG Jiao, LI Fengjie, YANG Zeyu, WANG Yanzhou, LIANG Zhiqing
Format: | Article |
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Diterbitkan: | Editorial Office of Journal of Third Military Medical University 2020-01-01 |
Deskripsi
Objective To investigate the expression of folate receptor 1(FOLR1) and mesothelin (MSLN) in epithelial ovarian cancer(EOC) and explore their clinical significance. Methods The data of clinical samples and transcriptome sequencing expression matrix of EOC were obtained from TCGA and GEO database(Ovarian Cancer TCGA, Provisional; GSE6008; GSE66957; GSE49997) to analyze the expressions of FOLR1 and MSLN in different tissues and their association with tumor staging and the prognosis of EOC. We also collected paraffin-embedded tissue samples of EOC(105 cases), ovarian borderline tumor(11 cases), and normal ovarian tissue(30 cases) from patients undergoing surgeries in our hospital between 2018 and 2019. The expression levels of FOLR1 and MSLN were detected by immunohistochemistry and their correlation with the clinicopathological characteristics of the patients was analyzed. Results Analysis of TCGA and GEO databases showed that the mRNA levels of FOLR1 and MSLN were significantly higher in EOC tissues than in normal ovarian tissues(P < 0.05), and was also higher in stage Ⅲ~Ⅳ than in stage Ⅰ~Ⅱ EOC(P < 0.05). Survival analysis showed that the patients with a high expression of FOLR1 had significantly longer overall survival(P < 0.05) and disease-free survival(P < 0.05), while the patients with a high expression of MSLN had significantly shortened overall survival(P < 0.05) and disease-free survival(P < 0.05). Immunohistochemical analysis showed that FOLR1 and MSLN proteins were lowly expressed in normal ovarian tissues, and their expressions increased moderately in borderline ovarian tumor and significantly in EOC tissues. The positive expression rates of FOLR1 and MSLN in EOC were 80.95% and 53.33%, respectively. The levels were of FOLR1 and MSLN differed significantly in different tissue types(P < 0.001), and their positive rates were significantly higher in stage Ⅲ~Ⅳ than in stage Ⅰ~Ⅱ EOC(P < 0.05). The positive rate of MSLN was significantly increased in patients with lymph node metastasis(P < 0.05). Subgroup survival analysis of TCGA database showed that patients with a low MSLN expression and a high FOLR1 expression(MLFH) at the mRNA level had the best prognosis, while those with a high MSLN expression and a low FOLR1 expression(MHFL) had the worst prognosis(median survival time 70.57 vs 25.85 months, P < 0.000 1); compared with the MLFL patients, the MHFL patients in the early stage(< 50 months) had a better prognosis, while beyond 50 months, the survival rate of the patients decreased, but the difference was not statistically significant. Conclusion In patients with EOC, a high expression of FOLR1 indicates a more favorable prognosis while a high expression of MSLN is associated with a poor prognosis. These 2 proteins may participate in the process of EOC, and their combined detection may help in prognostic evaluation of EOC.