TROP2、p-ERK1/2和Cyclin D1在胆囊癌组织中的表达及临床意义  

Expression of trophoblast cell-surface antigen 2,phosphorylated extracellular signal-regulated kinase 1/2,and cyclin D1 in gallbladder carcinoma tissue and related clinical significance

作　　者：李新星[1] 滕世峰 徐楷[1] 张言言 张卫刚[1] 张宪文[1] 姚骏[1] 姚厚山[1] 黄歆[1] 胡志前[1] 

机构地区：[1]第二军医大学附属长征医院普外一科,上海200030

出　　处：《临床肝胆病杂志》2017年第5期909-914,共6页Journal of Clinical Hepatology

基　　金：国家青年科学基金资助(8140101730)

摘　　要：目的探讨胆囊癌组织中人滋养层细胞表面抗原(TROP)2、磷酸化细胞外信号调节激酶(p-ERK)1/2和细胞周期蛋白D1(Cyclin D1)的表达及其与临床病理参数之间的关系,并分析其与胆囊癌患者预后的关系。方法搜集第二军医大学附属长征医院2005年6月-2010年6月确诊并获取病理标本的胆囊癌患者88例,采用免疫组化法检测88例胆囊癌组织及15例癌旁组织中TROP2、p-ERK1/2和Cyclin D1蛋白的表达。计数资料采用χ~2检验,Spearman检验法分析TROP2、p-ERK1/2和Cyclin D1间相关性;单因素和多因素Cox回归分析胆囊癌患者预后的影响因素;Kaplan-Meier法绘制患者的生存曲线。结果 TROP2、p-ERK1/2和Cyclin D1蛋白在胆囊癌组织中的阳性表达率分别为74.30%、58.40%和55.30%,明显高于癌旁组织中的表达(5.42%、35.67%和39.87%)(P值均<0.05)。TROP2、p-ERK1/2和Cyclin D1蛋白的表达与胆囊结石、肿瘤直径、分化程度、血管神经侵犯、淋巴结转移、手术方式及TNM分期相关(χ~2=4.300~53.315,P值均<0.05)。TROP2与p-ERK1/2、Cyclin D1的表达呈正相关(rs值分别为0.402、0.742,P值均<0.001),且p-ERK1/2与Cyclin D1的表达也呈正相关(rs=0.242,P=0.023)。多因素生存分析提示,TROP2的阳性表达是患者3年生存率的独立危险因素(相对危险度=2.412,95%可信区间:1.186~5.126,P=0.010)。结论 TROP2的高表达可能是胆囊癌恶性进展的重要原因,高表达的TROP2可能介导p-ERK1/2和Cyclin D1的高表达,导致胆囊癌恶性进展。TROP2是判断胆囊癌患者预后的独立危险因素,有可能是临床干预的有效靶点。Objective To investigate the expression of human trophoblast cell - surface antigen 2 （ TROP2 ）, phosphorylated extracellular signal - regulated kinase 1/2 （ p - ERK1/2）, and cyclin D1 in gallbladder carcinoma tissue and their correlation with clinicopathological pa- rameters, as well as their association with the prognosis of patients with gallbladder carcinoma. Methods A total of 88 patients who were di- agnosed with gallbladder carcinoma in Changzheng Hospital, Second Military Medical University, from June 2005 to June 2010 were en- rolled, and their pathological specimens were obtained, lmmunohistochemistry was used to measure the expression of TROP2, p - ERK1/2, and cyclin D1 in 88 gallbladder carcinoma tissue samples and 15 adjacent tissue samples. The chi - square test was used for comparison of categorical data between groups, and the Spearman method was used to investigate the correlation between any two parameters of TROP2, p - ERK1/2, and eyclin D1 ; univariate and multivariate Cox regression analyses were used to analyze the influencing factors for the progno- sis of patients with gallbladder carcinoma; the Kaplan - Meier method was used to plot their survival curves. Results The positive rates of TROP2, p - ERK1/2, and cyclin D1 in gallbladder cancer tissue were 74.30%, 58.40%, and 55.30% , respectively, significantly higher than those in adjacent tissue （5.42%, 35.67% and 39.87%, respectively） （ P 〈 0.05 ）. The expression of TROP2, p - ERK1/2, and cy- clin D1 was associated with gallstones, tumor diameter, degree of tumor differentiation, vascular and perineural invasion, lymph node metas- tasis, surgical procedure, and TNM stage 0（2 =4. 300 -53. 315, all P 〈0. 05）. The expression of TROP2 was positively correlated with that of p - ERK1/2 and cyclin D1 （ rs = 0.402 and 0.742, both P 〈 0.001 ）, and the expression of p - ERK1/2 was also positively correla- ted with that of cyclin DI （r^2 = 0.242, P = 0.023 ）. The multivariate survival analysis showed that positive exp

关 键 词：胆囊肿瘤 人滋养层细胞表面抗原2 磷酸化细胞外信号调节激酶1/2 细胞周期蛋白D1 预后 

分 类 号：R735.8[医药卫生—肿瘤]