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中华妇幼临床医学杂志(电子版) ›› 2021, Vol. 17 ›› Issue (04) : 402 -409. doi: 10.3877/cma.j.issn.1673-5250.2021.04.005

论著

XPO4、MAP2K4及ZIC1在子宫内膜癌组织表达及其对子宫内膜癌患者预后评估价值
王丽娜1,1, 刘银萍2,2, 赵绍杰1,†,1()   
  • 收稿日期:2020-08-27 修回日期:2021-06-17 出版日期:2021-08-01
  • 通信作者: 赵绍杰

Expression of XPO4, MAP2K4 and ZIC1 in endometrial cancer tissues and prognostic value in endometrial cancer patient

Lina Wang1,1, Yinping Liu2,2, Shaojie Zhao1,1,†()   

  • Received:2020-08-27 Revised:2021-06-17 Published:2021-08-01
  • Corresponding author: Shaojie Zhao
  • Supported by:
    National Natural Science Foundation of China(81902628)
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引用本文：

王丽娜, 刘银萍, 赵绍杰. XPO4、MAP2K4及ZIC1在子宫内膜癌组织表达及其对子宫内膜癌患者预后评估价值[J/OL]. 中华妇幼临床医学杂志(电子版), 2021, 17(04): 402-409.

Lina Wang, Yinping Liu, Shaojie Zhao. Expression of XPO4, MAP2K4 and ZIC1 in endometrial cancer tissues and prognostic value in endometrial cancer patient[J/OL]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2021, 17(04): 402-409.

目的

探讨输出蛋白(XPO)4、丝裂原活化蛋白激酶(MAP2K)4及小脑锌指结构蛋白(ZIC)1在子宫内膜癌(EC)组织中的表达及其对EC患者的预后评估价值。

方法

选择2017年6月至2018年6月，无锡市妇幼保健院、复旦大学附属中山医院青浦分院收治的147例EC患者为研究对象。采用免疫组化染色法检测患者EC组织及癌旁正常组织XPO4、MAP2K4、ZIC1表达水平。采用χ2检验，对患者EC组织及癌旁正常组织XPO4、MAP2K4、ZIC1阳性率，以及不同临床病理特征患者EC组织XPO4、MAP2K4、ZIC1阳性率进行比较。采用Two-stage检验，对EC组织XPO4、MAP2K4、ZIC1呈阳性与呈阴性患者的3年总体生存(OS)率进行比较。本研究遵循的程序经过无锡市妇幼保健院、复旦大学附属中山医院青浦分院伦理委员会批准(审批文号：20160803、20160502)。

结果

①本组患者EC组织XPO4、MAP2K4阳性率分别为34.7%(51/147)、38.1%(56/147)，显著低于癌旁正常组织的66.7%(98/147)与72.8%(107/147)，并且差异均有统计学意义(χ2＝30.060、35.812，P<0.001)。本组患者EC组织ZIC1阳性率为72.1%(106/147)，显著高于癌旁正常组织的40.1%(59/147)，并且差异亦有统计学意义(χ2＝30.512、P<0.001)。②不同年龄、EC直径及绝经与否患者的EC组织XPO4、MAP2K4、ZIC1阳性率比较，差异均无统计学意义(P>0.05)。不同国际妇产科联盟(FIGO)临床分期、组织病理学分级、子宫肌层侵犯程度及淋巴结转移与否患者EC组织XPO4、MAP2K4、ZIC1阳性率分别比较，差异均有统计学意义(P<0.05)。③本组EC组织XPO4、MAP2K4呈阴性患者的3年OS率分别为42.7%、38.5%，均显著低于XPO4、MAP2K4呈阳性者的68.6%、71.4%，并且差异均有统计学意义(χ2＝8.960、P＝0.003，χ2＝15.077、P<0.001)。EC组织ZIC1呈阳性患者3年OS率为35.8%，显著低于ZIC1呈阴性者的68.3%，并且差异亦有统计学意义(χ2＝12.579、P<0.001)。

结论

在EC组织中，XPO4、MAP2K4呈低表达，而ZIC1则呈高表达。XPO4、MAP2K4、ZIC1表达水平与患者组织病理学分级、淋巴结转移、FIGO临床分期、子宫肌层侵犯及3年OS率显著相关，其在评估EC患者发病、进展及预后中具有一定价值。

关键词: 子宫内膜肿瘤, 输出蛋白4, 丝裂原活化蛋白激酶4, 小脑锌指结构蛋白1, 预后, 女(雌)性
Objective

To explore expression of exportin (XPO)4, mitogen-activated protein kinase (MAP2K)4 and zinc finger protein of cerebellum (ZIC)1 in endometrial cancer (EC) tissues and their prognostic values in EC patient.

Methods

From June 2017 to June 2018, a total of 147 EC patients admitted to Wuxi Maternal and Child Health Hospital and Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University were selected as research subjects. Expression levels of XPO4, MAP2K4 and ZIC1 in EC tissues and adjacent normal tissues of EC patients were detected by immunohistochemical staining method. Positive rates of XPO4, MAP2K4, and ZIC1 in EC tissues and adjacent normal tissues of EC patients, as well as positive rates of XPO4, MAP2K4, and ZIC1 in EC tissues of EC patients with different clinicopathological characteristics were compared by chi-square test. Two-stage test was used to compare 3-year overall survival (OS) rates of EC patients with XPO4, MAP2K4, ZIC1 positive expression and negative expression in EC tissues. This study was approved by the Ethics Committee of Wuxi Maternal and Child Health Hospital and Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University (approval No. 20160803, 20160502).

Results

①The positive rates of XPO4 and MAP2K4 in EC tissues of EC patients were 34.7% (51/147) and 38.1% (56/147) respectively, which were statistically lower than those in adjacent normal tissues 66.7% (98/147) and 72.8% (107/147), and both differences were statistically significant (χ2=30.060, 35.812; P<0.001). The positive rate of ZIC1 in EC tissues of EC patients was 72.1% (106/147), which was statistically higher than that in adjacent normal tissues 40.1% (59/147), and the difference was statistically significant (χ2=30.512, P<0.001). ②The positive rates of XPO4, MAP2K4, and ZIC1 in EC tissues of EC patients with different age, EC diameter and menopausal or not were compared, and the differences were not statistically significant (P>0.05). While there were statistically significant differences in the positive rates of XPO4, MAP2K4 and ZIC1 in EC tissues of EC patients with different International Federation of Obstetrics and Gynecology (FIGO) stages, histopathological grades, myometrial invasion degree, and lymph node metastasis (P<0.05). ③The 3-year OS rates of EC patients with negative expression of XPO4 and MAP2K4 were 42.7% and 38.5% respectively, which were statistically lower than those of patients with positive expression of XPO4 and MAP2K4 68.6% and 71.4%, and both differences were statistically significant (χ2=8.960, P=0.003; χ2=15.077, P<0.001). The 3-year OS rate of EC patients with positive expression of ZIC1 was 35.8%, which was statistically lower than that of patients with ZIC1 negative expression, and the difference was statistically significant (χ2=12.579, P<0.001).

Conclusions

XPO4 and MAP2K4 are lowly expressed, and ZIC1 is highly expressed in EC tissues. Expression levels of XPO4, MAP2K4 and ZIC1 are related to the histopathological grade, lymph node metastasis, FIGO stage, myometrial invasion, and 3-year OS rate of EC patients, and they have certain values in assessing the development, progression and prognosis of EC patients.

Key words: Endometrial neoplasms, Exportin-4, Mitogen-activated protein kinase 4, Zinc finger protein of cerebellum 1, Prognosis, Female
表1 本组EC患者EC组织及癌旁正常组织的XPO4、MAP2K4、ZIC1阳性率比较[例数(%)]
组别 例数 XPO4 MAP2K4 ZIC1
EC组织 147 51(34.7) 56(38.1) 106(72.1)
癌旁正常组织 147 98(66.7) 107(72.8) 59(40.1)
χ2值   30.060 35.812 30.512
P值   <0.001 <0.001 <0.001
图1 本组1例EC患者(38岁，FIGO分期为Ⅱ期，伴淋巴结转移)EC组织及癌旁正常组织XPO4、MAP2K4、ZIC1免疫组化检测结果(图1A：EC组织XPO4检测结果；图1B：癌旁正常组织XPO4检测结果；图1C：EC组织MAP2K4检测结果；图1D：癌旁正常组织MAP2K4检测结果；图1E：EC组织ZIC1检测结果；图1F：癌旁正常组织ZIC1检测结果)(免疫组化染色，高倍)
表2 本组EC患者的EC组织XPO4、MAP2K4、ZIC1阳性率比较[例数(%)]
类别 例数 XPO4 MAP2K4 ZIC1
阳性 χ2值 P值 阳性 χ2值 P值 阳性 χ2值 P值
年龄(岁)     0.027 0.869   0.098 0.754   0.529 0.467
  <50 27 9(33.3)     11(40.7)     21(77.8)    
  ≥50 120 42(35.0)     45(37.5)     85(70.8)    
EC直径(cm)     0.061 0.804   0.013 0.910   0.037 0.847
  <4.0 77 26(33.8)     29(37.7)     55(71.4)    
  ≥4.0 70 25(35.7)     27(38.6)     51(72.9)    
绝经     0.005 0.942   0.034 0.853   0.028 0.866
  否 38 13(34.2)     14(36.8)     27(71.1)    
  是 109 38(34.9)     42(38.5)     79(72.5)    
FIGO分期(期)     6.565 0.010   6.491 0.011   9.525 0.002
  Ⅰ~Ⅱ 115 46(40.0)     50(43.5)     76(66.1)    
  Ⅲ 32 5(15.6)     6(18.8)     30(93.8)    
组织病理学分级(级)     3.963 0.047   5.236 0.022   6.032 0.014
  G1~G2 127 48(37.8)     53(41.7)     87(68.5)    
  G3 20 3(15.0)     3(15.0)     19(95.0)    
子宫肌层侵犯(%)     8.434 0.004   9.046 0.003   15.640 <0.001
  <50 105 44(41.9)     48(45.7)     66(62.9)    
  ≥50 42 7(16.7)     8(19.0)     40(95.2)    
淋巴结转移     9.407 0.002   9.884 0.002   8.746 0.003
  否 107 45(42.1)     49(45.8)     70(65.4)    
  是 40 6(15.0)     7(17.5)     36(90.0)    
图2 本组EC组织XPO4、MAP2K4、ZIC1呈阳性与呈阴性EC患者的OS曲线分析(图2A：XPO4呈阳性与呈阴性EC患者OS曲线；图2B：MAP2K4呈阳性与呈阴性EC患者OS曲线；图2C：ZIC1呈阳性与呈阴性EC患者OS曲线)
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