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中华妇幼临床医学杂志(电子版) ›› 2015, Vol. 11 ›› Issue (03) : 323 -328. doi: 10.3877/cma.j.issn.1673-5250.2015.03.008

所属专题： 文献；

论著

膜相关蛋白Numb在上皮性卵巢癌中的表达及其与耐药相关蛋白P糖蛋白、多药耐药相关蛋白1的关系
敬宏1, 郑艾2, 牛晓宇2,*,*()   
  1. 1. 610041　成都，四川大学华西第二医院妇产科（目前工作单位为四川卫生康复职业学院护理系）
    2. 610041　成都，四川大学华西第二医院妇产科
  • 收稿日期:2015-01-09 修回日期:2015-04-30 出版日期:2015-06-01
  • 通信作者: 牛晓宇

Expression level of membrane-associated proteins Numb in epithelial ovarian cancer and its relationship with drug resistance P-glycoprotein and multidrug resistance-associated protein 1

Hong Jing1, Ai Zheng2, Xiaoyu Niu2()   

  1. 1. Department of Gynaecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
  • Received:2015-01-09 Revised:2015-04-30 Published:2015-06-01
  • Corresponding author: Xiaoyu Niu
  • About author:
    Corresponding author: Niu Xiaoyu, Email:
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敬宏, 郑艾, 牛晓宇. 膜相关蛋白Numb在上皮性卵巢癌中的表达及其与耐药相关蛋白P糖蛋白、多药耐药相关蛋白1的关系[J/OL]. 中华妇幼临床医学杂志(电子版), 2015, 11(03): 323-328.

Hong Jing, Ai Zheng, Xiaoyu Niu. Expression level of membrane-associated proteins Numb in epithelial ovarian cancer and its relationship with drug resistance P-glycoprotein and multidrug resistance-associated protein 1[J/OL]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2015, 11(03): 323-328.

目的

探讨膜相关蛋白Numb在上皮性卵巢癌(EOC)中的表达及其与耐药相关蛋白P糖蛋白(P-gp)及多药耐药相关蛋白(MRP)-1的关系。

方法

选择2012年1月至2014年6月在四川大学华西第二医院妇科住院治疗的136例卵巢肿瘤患者及同期因子宫病变而无卵巢肿瘤行子宫及双侧附件切除的22例患者为研究对象，根据术后摘除卵巢组织的病理学检查结果，将其分为EOC组(n＝92)、卵巢交界性肿瘤(BOT)组(n＝23)、卵巢良性肿瘤组(n＝21)及正常卵巢组(n＝22)。采用免疫组化SP法检测患者卵巢组织的Numb蛋白、P-gp及MRP-1表达水平。统计学分析Numb蛋白在4组中及在EOC组不同临床特征患者中的阳性表达率差异，EOC组患者3种蛋白阳性表达率差异及相关关系，以及与化疗敏感及耐药的关系。本研究遵循的程序符合四川大学华西第二医院人体试验委员会制定的伦理学标准，得到该委员会批准，并与受试者签署临床研究知情同意书。4组患者年龄，身高及体质量等一般临床资料比较，差异无统计学意义(P>0.05)。

结果

①卵巢组织中Numb蛋白阳性表达率比较：EOC组较卵巢良性肿瘤组及正常卵巢组高，BOT组较正常卵巢组高，且差异均有统计学意义(P<0.05)；而EOC组与BOT组比较、BOT组与卵巢良性肿瘤组比较及卵巢良性肿瘤组与正常卵巢组比较，差异则均无统计学意义(P>0.05)。②EOC组不同临床特征患者卵巢组织Numb蛋白阳性表达率比较：FIGOⅠ～Ⅱ期患者显著低于Ⅲ～Ⅳ期患者，无淋巴结转移患者显著低于有淋巴结转移患者，且差异均有统计学意义(P<0.05)；而不同年龄、临床病理学类型、组织病理分级及残留灶大小之间比较，差异则无统计学意义(P>0.05)。③EOC组患者卵巢组织的Numb蛋白与P-gp阳性表达率比较，差异无统计学意义(P>0.05)，二者表达无相关性(r＝0.117，P＝0.109)；而Numb蛋白阳性表达率较MRP-1低，且差异有统计学意义(P<0.05)，二者表达呈正相关关系(r＝0.179，P＝0.013)。④EOC组完成随访的78例患者中，化疗敏感者为65例，化疗耐药者为13例。二者间Numb蛋白、P-gp及MRP-1阳性表达率比较，差异均无统计学意义(P>0.05)；在化疗敏感患者或化疗耐药患者中，此3种蛋白阳性表达率两两分别比较，差异亦均无统计学意义(P>0.05)。

结论

Numb基因在卵巢肿瘤的发生机制中可能作为癌基因存在。Numb蛋白与卵巢肿瘤细胞增殖、侵袭和转移有关。Numb蛋白与MRP-1表达相关，但Numb蛋白能否与P-gp及MRP-1一样，成为化疗耐药性的检测指标，尚需扩大样本量进一步研究证实。

关键词: 卵巢肿瘤, Numb蛋白，人类的, P糖蛋白, 多药耐药相关蛋白1, 免疫组织化学, 抗药性
Objective

To explore the expression level of membrane-associated protein Numb in epithelial ovarian cancer(EOC) and its relationship with drug resistance P-glycoprotein(P-gp) and multidrug resistance-associated protein(MRP)-1.

Methods

A total of 136 patients who had ovarian tumors and 22 patients who had hysterectomy and bilateral salpingooophorectomy only for the lesion in uterus from January 2012 to June 2014 in department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University were chosen as study subjects.According to the histopathologic examination results of ovaries tissues, they were divided into EOC group(n=92), borderline ovarian tumor(BOT) group(n=23), ovarian benign tumor group(n=21) and normal ovary group(n=22). Expression levels of Numb protein, P-gp and MRP-1 in ovarian tissues were detected by immunohistochemical SP method, the positive expression rates differences of Numb protein among 4 groups and in patients of different clinical characteristics in EOC group were analyzed statistically. The positive expression rates differences of these 3 kinds of protein and their correlation in EOC group, and the relationship with chemotherapy sensitive and chemotherapy resistance were analyzed statistically.This study was approved by the ethic committee of West China Second University Hospital, Sichuan University, and consent forms were signed by all the patients.There were no significant differences among 4 groups in general clinical data, such as age, body height and body mass, etc.(P>0.05).

Results

①The positive expression rate of Numb protein in EOC group was higher than that in benign tumor or normal ovary group, also Numb protein positive expression rate in BOT group was higher than that in normal ovary group, and the differences were statistically significant(P<0.05). However, there were no significant differences of Numb protein positive expression rates neither between EOC group and BOT group, nor between BOT group and ovarian benign tumor group, nor between ovarian benign tumor group and normal ovary group(P>0.05). ②Comparison of Numb protein positive expression rate in ovarian tissue in EOC group: the positive expression rate in FIGO stageⅠ-Ⅱ was lower than that in stage Ⅲ-Ⅳ, also the same in no lymph nodes metastasis compared with lymph nodes invasion, and the differences were statistically significant(P<0.05). While there were no significant differences among different age, clinical pathology types, pathological grades and residual tumor size(P>0.05). ③There was no significant difference between Numb protein and P-gp positive expression rate in EOC group(P>0.05), also there was no correlation between them(r=0.117, P=0.109). However, the positive expression rate of Numb protein was lower than that of MRP-1, and the difference was significant(P<0.05), also they were positively correlated(r=0.179, P=0.013). ④A total of 78 EOC patients were followed up successfully for chemoresistance, among them, 65 patients were chemotherapy sensitive and 13 patients were chemotherapy resistant.There were no significant differences between chemotherapy sensitive and resistant patients in positive expression rates of Numb protein, P-gp and MRP-1(P>0.05). Also, there was no significant difference of positive expression rate between any two of these 3 kinds of protein in chemotherapy sensitive or resistant patients(P>0.05).

Conclusions

Numb gene might be an oncogene in the development of ovarian neoplasms.Numb protein may be related with proliferation, invasion and metastasis of ovarian neoplasms tumor cell.The expression of Numb protein is correlated with the expression of MRP-1, but a further large sample research is needed to be done to certify whether Numb protein can act as a predictive parameter of chemotherapy sensation.

Key words: Ovarian neoplasms, Numb protein, human, P-glycoprotein, Multidrug resistance-associated protein 1, Immunohistochemistry, Drug resistance
图1 3种蛋白在上皮性卵巢癌中的表达（图1A：Numb蛋白；图1B：P-gp；图1C：MRP-1；DAB显色×400）
Figure 1 Expressions of 3 kinds of protein in epithelial ovarian carcer(Figure 1A:Numb protein;Figure 1B:P-gp;Figure 1C:MRP-1; DAB chromogenic×400)
表1 不同临床特征EOC组患者的Numb蛋白阳性表达率比较[n(%)]
Table 1 Comparison of positive expression rates of Numb proteins among patients of different clinical conditions in EOC group[n(%)]
临床特征 例数 Numb蛋白阳性表达率 χ2值 P值
年龄(岁) ? ? 0.523 0.470
? ≤40 16 9(56.2) ? ?
? >40 76 50(65.8) ? ?
FIGO分期(期) ? ? 5.686 0.017
? Ⅰ～Ⅱ 23 10(43.5) ? ?
? Ⅲ～Ⅳ 69 49(71.0) ? ?
临床病理学类型 ? ? 0.303 0.960
? 浆液性癌 55 35(63.6) ? ?
? 黏液性癌 10 7(70.0) ? ?
? 子宫内膜样癌 7 4(57.1) ? ?
? 透明细胞腺癌 6 4(66.7) ? ?
? 混合性腺癌 14 9(64.3) ? ?
组织病理分级 ? ? 0.974 0.324
? 高分化 10 5(50.0) ? ?
? 中、低分化 82 54(65.8) ? ?
淋巴结转移 ? ? 5.267 0.022
? 无 75 44(58.7) ? ?
? 有 17 15(88.2) ? ?
残留灶直径(cm) ? ? 0.557 0.455
? ≤2 86 56(65.1) ? ?
? >2 6 3(50.0) ? ?
表2 化疗敏感及耐药患者之间3种蛋白阳性表达率比较及3种蛋白在化疗敏感或耐药患者中阳性表达率比较[例数(%)]
Table 2 Comparison of positive expression rates of Numb，P-gp and MRP-1 between chemotherapy sensitive and chemotherapy resistance patients，and comparison of positive expression rates among these 3 kinds of protein in chemotherapy sensitive patients or chemotherapy resistant patients[case(%)]
化疗结果 例数 Numb蛋白阳性表达率 P-gp阳性表达率 MRP-1阳性表达率
化疗敏感 65 45(69.2) 49(75.4) 52(80.0)
化疗耐药 13 6(46.2) 9(69.2) 10(76.9)
χ2值 ? 2.549 0.215 0.063
P值 ? 0.110 0.643 0.802
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