GLI1及Shh在卵巢型子宫内膜异位症恶变过程中的表达及其意义  

Expression and significance of GLI1 and Shh in the malignant transformation of ovarian endometriosis

作　　者：赵飞[1] 于新平 赵涵[1] 宋冰冰 吕广伟 张世红[3] 王黎明[1] Zhao Fei;Yu Xinping;Zhao Han;Song Bingbing;Lyu Guangwei;Zhang Shihong;Wang Liming(Department of Gynecology,Qingdao University Affiliated Hospital,Qingdao 266003,China;Department of Gynecology,Shandong Weihai Women′s and Children′s Hospital,Weihai 264299,China;Department of Obstetrics and Gynecology,Shandong Weihai Municipal Hospital,Weihai 264299,China)

机构地区：[1]青岛大学附属医院妇科,青岛266003 [2]山东省威海市妇幼保健院妇科,威海264299 [3]山东省威海市立医院妇产科,威海264299

出　　处：《中华妇产科杂志》2022年第2期125-132,共8页Chinese Journal of Obstetrics and Gynecology

基　　金：青岛西海岸新区2019年度科技项目(2019-54)。

摘　　要：目的探讨神经胶质瘤相关基因同源蛋白1(GLI1)及超音刺猬蛋白(Shh)在卵巢型子宫内膜异位症(EM)恶变过程中的表达及其临床意义。方法收集2000年4月—2018年4月在青岛大学附属医院及山东省威海市立医院行手术治疗的EM相关性卵巢上皮性癌(EAOC,即卵巢型EM恶变)患者50例(EAOC组),其年龄为(49±7)岁;另收集同期的卵巢异位子宫内膜非典型增生(aEM)患者35例(aEM组),其年龄为(44±9)岁,卵巢型EM患者50例(EM组),其年龄为(37±8)岁。实时荧光定量PCR技术及免疫组化EnVision二步法分别检测3组病变组织中GLI1、Shh mRNA和蛋白的表达,比较其在卵巢型EM恶变过程中的表达差异,分析GLI1与Shh表达的相关性,并分析GLI1及Shh表达与EAOC患者临床病理特征、预后的关系。结果(1)实时荧光定量PCR技术检测显示,EM组、aEM组、EAOC组病变组织中GLI1 mRNA的表达水平分别为1.77±0.40、3.54±0.44、7.80±0.24,Shh mRNA的表达水平分别为0.95±0.21、3.14±0.35、5.41±0.31,EAOC组GLI1、Shh mRNA的表达水平均显著高于EM组、aEM组(P均<0.01),EM组与aEM组分别比较,差异也均有统计学意义(P均<0.01)。免疫组化EnVision二步法检测显示,EM组、aEM组、EAOC组病变组织中,GLI1蛋白的高表达率分别为32%(16/50)、57%(20/35)及66%(33/50),Shh蛋白的高表达率分别为20%(10/50)、49%(17/35)、54%(27/50),3组分别比较,差异均有统计学意义(P均<0.01)。EAOC组织中,GLI1 mRNA与Shh mRNA的表达呈显著正相关(r=0.721,P<0.01),GLI1蛋白与Shh蛋白的表达也呈显著正相关(r=0.608,P=0.001)。(2)GLI1蛋白表达与EAOC患者的血清癌抗原125(CA125)水平、国际妇产科联盟(FIGO)分期、淋巴结转移状态、铂敏感性显著有关(P均<0.05);Shh蛋白表达与EAOC患者的FIGO分期、淋巴结转移状态均显著有关(P均<0.05)。logistic回归模型多因素分析显示,FIGO分期Ⅲ~Ⅳ期、血清CA_(125)≥35 kU/L、GLI1蛋白高表达是影响EAOC患者预后的独立因素(P�Objective To investigate the expression levels and clinical significance of glioma-associated oncogene homolog 1(GLI1)and sonic hedgehog signaling molecule(Shh)in the malignant transformation of ovarian endometriosis(EM).Methods The expressions of GLI1 and Shh were detected by real-time reverse transcription(RT)-polymerase chain reaction(PCR)and EnVision method in 50 cases of ovarian EM tissues,35 cases of atypical endometriosis(aEM)and 50 cases of endometriosis-associated ovarian cancer(EAOC).The expression differences of two molecular markers in the malignant transformation of ovarian EM were compared,and the relationships between two molecular markers and the clinicopathological features and prognosis of EAOC were analyzed.Results(1)RT-PCR showed that the expression levels of GLI1 mRNA in EM,aEM and EAOC group were 1.77±0.40,3.54±0.44,and 7.80±0.24,respectively.The expression levels of Shh mRNA were 0.95±0.21,3.14±0.35,and 5.41±0.31,respectively.GLI1 and Shh mRNA in EAOC group were significantly higher than those in EM and aEM group(all P<0.01),and there were statistically significant differences between EM and aEM group(all P<0.01).The percentages of GLI1 in ovarian EM,aEM and EAOC were 32%(16/50),57%(20/35),and 66%(33/50),respectively,meanwhile,the positive expression rates of Shh were 20%(10/50),49%(17/35),and 54%(27/50),respectively(all P<0.01).GLI1 mRNA expression was positively correlated with Shh mRNA expression in EAOC tissues(r=0.721,P<0.01).The expressions of GLI1 protein were proportionated to Shh protein in EAOC tissues(r=0.608,P=0.001).(2)The expression of GLI1 was significantly related to the International Federation of Gynecology and Obstetrics(FIGO)stage,cancer antigen 125(CA_(125))levels,lymph node metastasis,and Platinum resistance in EAOC patients(all P<0.05).The expression of Shh were related to FIGO stage and lymph node metastasis in EAOC patients(all P<0.05).Logistic regression analysis showed that GLI1 expression was an independent risk factor for poor prognosis in EAOC patients(P<

关 键 词：子宫内膜异位症 卵巢疾病 卵巢肿瘤 锌指蛋白GLI1 猬蛋白质类 

分 类 号：R711.71[医药卫生—妇产科学]