卵巢恶性肿瘤组织叶酸结合蛋白表达检测及其临床意义

Detection of folate binding protein and its clinical significance in ovarian cancers

背景与目的:叶酸结合蛋白(folate binding protein,FOLR1)又称为叶酸受体蛋白,对细胞分裂、增殖和生长有着非常重要的作用。FOLR1在正常组织中表达较低,但在卵巢癌中存在过度表达。本研究探讨卵巢恶性肿瘤组织中FOLR1的表达及其临床意义。方法:采用Western blot检测80例卵巢恶性肿瘤组织、50例卵巢良性肿瘤组织及30例正常卵巢组织中的FOLR1表达情况,分析其与卵巢恶性肿瘤临床病理及多药耐药的相关性。结果:FOLR1在正常卵巢组织、卵巢良性肿瘤组织和卵巢恶性肿瘤组织中的表达量依次增高(P<0.01)。FOLR1在卵巢恶性肿瘤临床分期中Ⅰ～Ⅱ期的表达量低于Ⅲ～Ⅳ期(P<0.05)。FOLR1在铂类药物耐药型卵巢恶性肿瘤中的表达量低于铂类药物敏感型(P<0.01);治疗后肿瘤进展者的表达量低于缓解者(P<0.01)。FOLR1在黏液性肿瘤中的表达量低于浆液性肿瘤(P<0.05),恶性卵巢肿瘤有淋巴结和远处器官转移的高于无转移者(P<0.05),其表达量与患者的不同肿瘤病理分类、是否有大网膜转移和腹水量无明显相关(P>0.05)。取FOLR1表达量界值为3.115时来判断卵巢肿瘤性质,ROC曲线的Youden指数最大,卵巢恶性肿瘤FOLR1表达量的高低与中位生存时间长短差异无明显相关(P>0.05),Cox模型多因素分析显示,FOLR1表达量不是影响患者生存预后的独立因素。结论:FOLR1可作为一种新型的卵巢恶性肿瘤早期诊断标志物,并可成为判断卵巢恶性肿瘤多药耐药潜在标志之一。

Background and purpose：Folate binding protein（FOLR1）,also known as folate receptor protein,plays a key role in division,proliferation and growth of cells.It was less expressed in normal tissues,but over-expression often existed in ovarian cancer.Our study aimed to explore the expression level of FOLR1 and its clinical significance in ovarian cancer.Methods：Western blot was used to detect the expression levels of FOLR1 in 80 ovarian cancer tissues,50 benign ovarian tumor tissues and 30 normal ovarian tissues,and its association with clinical pathology and multidrug resistance（MDR） of ovarian cancers was analyzed.Results：The expression levels of FOLR1 increased orderly in normal ovarian tissues,benign ovarian tumor tissues and ovarian cancer tissues,and the difference was statistically significant（P0.01）.For ovarian cancer,the expression levels of FOLR1 in clinical stage Ⅰ-Ⅱ were higher than that of stage Ⅲ-Ⅳ,and the difference was statistically significant（P0.05）.For ovarian cancer tissues,the FOLR1 levels of the platinum-resistant were less than the platinum-sensitive,and the difference was statistically significant（P0.01）.After chemotherapy,the FOLR1 levels of progressive ovarian cancer tissues were lower than those in remission,and the difference was statistically significant（P0.01）.For ovarian cancer tissues,the FOLR1 levels of the mucinous type were lower than that of the serous,and the difference was statistically significant（P0.05）.The FOLR1 levels of ovarian cancer with metastasis to lymph nodes and distant organs were higher than those without metastasis,and the difference was statistically significant（P0.05）.However,the FOLR1 levels had no significant association with pathological classification,amounts of ascites and metastasis to the omentum（P0.05）.ROC curve determining the FOLR1 levels associated nature of ovarian tumors demonstrated that the maximum Youden index was 3.115 and the FOLR1 levels showed no obvious correlation with median survival time（P0.05）.COX multivariate analysis denied the FOLR-α level as an independent prognostic factor.Conclusion：The FOLR1 levels of normal ovarian tissues and benign ovarian tumor tissues are lower than that of ovarian cancer tissues,which suggests FOLR1 could be a new biomarker for early diagnosis of ovarian carcinomas.Meanwhile,the FOLR1 levels in ovarian cancer tissues are low for the platinum-resistant but high for the platinum-sensitive,which suggests that FOLR1 is associated with multidrug resistance of ovarian carcinoma and could be a potential target for judging multidrug resistance.