叶酸受体蛋白1对卵巢癌患者的临床应用价值

Clinical Value of Folate Binding Protein 1 in Diagnosis and Chemotherapy Resistance Detection on Ovarian Cancer Patients

目的：探讨人卵巢组织叶酸受体蛋白1（FOLR1）表达量对卵巢癌患者诊断、疗效监测、化疗耐药和预后评估的临床应用价值。方法：93例卵巢癌患者（卵巢癌组）按照组织学分型分为黏液性癌组（n=37）、浆液性癌组（n=48）和内膜样癌组（n=8）;根据临床分期分为Ⅰ—Ⅱ期组（n=39）和Ⅲ—Ⅳ期组（n=54）;根据有无淋巴结或远处器官转移分为有转移组（n=21）和无转移组（n=72）;根据临床疗效分为完全缓解组（CR组,n=31）、部分缓解组（PR组,n=29）、病情稳定组（SD组,n=14）和病情进展组（PD组,n=19）;根据化疗耐药情况分为化疗耐药组（n=37）和化疗敏感组（n=56）。同期收治的卵巢良性肿瘤患者作为良性肿瘤组（n=60）。卵巢组织和功能正常妇女作为对照组（n=40）。采用Western Blotting技术检测各组卵巢组织FOLR1相对表达量,比较卵巢癌组、良性肿瘤组和对照组FOLR1水平差异,比较不同临床特征卵巢癌患者FOLR1水平差异,比较不同疗效和是否耐药卵巢癌患者FOLR1水平差异。通过FOLR1检测结果绘制ROC曲线,计算最佳临界值,并以此临界值评估卵巢癌患者60个月生存率。结果：与对照组比较,卵巢癌组和良性肿瘤组FOLR1相对表达量均显著升高（t=30.577、20.527,P〈0.01）,卵巢癌组较良性肿瘤组升高更明显（t=17.051,P〈0.01）。与浆液性癌组比较,黏液性癌组和内膜样癌组FOLR1相对表达量均显著降低（t=13.515、13.902,P〈0.01）,黏液性癌组与内膜样癌组FOLR1比较差异无统计学意义（t=0.187,P〉0.05）。Ⅲ—Ⅳ期组患者FOLR1表达水平显著高于Ⅰ—Ⅱ期组患者（t=10.834,P〈0.01）,有转移组FOLR1表达水平显著高于无转移组（t=10.335,P〈0.01）。与CR组患者比较,PR组、SD组和PD组患者FOLR1表达水平均依次升高,PR组高于CR组（t=16.42,P〈0.01）,SD组高于PR组（t=5.349,P〈0.01）,PD组更高于SD组（t=9.732,P〈0.01）。化疗敏感组患者FOLR1表达水平显著高于化疗耐药组（t=16.495,P〈0.01）。FOLR1≥3.184癌症患者60个月生存率仅为19.14%,而FOLR1〈3.184癌症患者60个月生存率达39.23%,两者差异有统计学意义（χ^2=4.715,P〈0.01）。结论：卵巢癌患者FOLR1表达量显著升高可以作为卵巢癌早期诊断、化疗耐药判断的生物标志物之一。

Objective：To explore the clinical value of folic acid-binding protein 1（FOLR1）in diagnosis,efficacy monitoring,chemotherapy resistance and prognosis assessment on ovarian cancer patients.Method：A total of 93 cases of ovarian cancer patients（malignant group）according to the histological classification were divided into the mucinous carcinoma group（n=37）,serous cancer group（n=48）,endometrial carcinoma group（n=8）,according to clinical stage were divided intoⅠ-Ⅱ Group（n=39）and Ⅲ-Ⅳ group（n=54）,according to whether lymph node or distant organ metastasis were divided into two groups（n=21and n=72）,according to the clinical efficacy were divided into CR group（n=31）,PR group（n=29）,SD group（n=14）and PD group（n=19）,according tothe resistance of chemotherapy were divided into chemotherapy resistant group（n=37）and chemotherapy sensitivity（n=56）.Another 60 cases of ovarian benign tumor patients were selected as benign group and 40 cases of normal ovarian women as control group.FOLR1 relative expression level in the ovarian tissues of each group were detected by Western blot,the level of FOLR1 in ovarian cancer group,benign tumor group and control group were compared,the level of FOLR1 in different clinical features of ovarian cancer patients were compared,the level of FOLR1 in different curative effect and drug resistant ovarian cancer were compared.The ROC curve was drawn by FOLR1 test,and the optimal critical value was calculated,and the survival rate of patients with ovarian cancer was evaluated by the critical value of 60 months.Results：FOLR1relative expression level in control group was（1.774±0.138）,benign group was（3.084±0.387）,malignant group was（4.795±0.617）,the relative expression of FOLR1 in malignant group was significantly higher than that in benign group and control group,the relative expression of FOLR1 in benign group was significantly higher than that in control group（P〈0.01）.Serous carcinoma FOLR1 expression level was significantly higher than that of mucinous carcinoma and endometrial cancer（P〈0.01）,Ⅲ-Ⅳ stage of varian cancer FOLR1 expression level was significantly higher than those inⅠ-Ⅱstage（P〈0.01）,lymph node or distant organ metastasis FOLR1 expression level was significantly higher than those without metastasis（P〈0.01）.The curative effect of CR,PR,SD,PD patients with FOLR1 expression levels were increased,the differences between each groups with statistically significant（P〈0.05）.The level of FOLR1 expression in chemotherapeutic drug resistance ovarian cancer patients was significantly lower in chemotherapy sensitivity patients（P〈0.01）.With FOLR1 positive and negative as the observation index,the 5year survival rate of FOLR1 positive group was 19.1%,and 39.2%in FOLR1 negative group,two group 5year survival rate with statistically significant（χ^2=4.715,P〈0.01）.Conclusion：FOLR1in ovarian cancer were significantly increased which can be used as a biomarker for early diagnosis and chemotherapy resistance of ovarian cancer.