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

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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 (TROP) 2, phosphorylated extracellular signal-regulated kinase (p-ERK) 1/2 and cyclin D1 in gallbladder carcinoma and its relationship with clinicopathological parameters Between the relationship and analysis of the prognosis of patients with gallbladder cancer. Methods Eighty-eight patients with gallbladder carcinoma diagnosed and pathologically collected from June 2005 to June 2010 were recruited from Changzheng Hospital affiliated to Second Military Medical University. The expression of TROP2 in 88 cases of gallbladder carcinoma and 15 cases of paracancerous tissues were detected by immunohistochemistry. p-ERK1 / 2 and Cyclin D1 protein expression. Counting data were analyzed by χ ~ 2 test, Spearman test was used to analyze the correlation between TROP2, p-ERK1 / 2 and Cyclin D1. The prognostic factors of gallbladder carcinoma were analyzed by one-way and multi-factor Cox regression analysis. Kaplan- curve. Results The positive rates of TROP2, p-ERK1 / 2 and Cyclin D1 in gallbladder carcinomas were 74.30%, 58.40% and 55.30%, respectively, which were significantly higher than those in paracancerous tissues (5.42%, 35.67% and 39.87% ) (All P <0.05). The expressions of TROP2, p-ERK1 / 2 and Cyclin D1 were associated with gallstones, tumor diameter, differentiation degree, vascular invasion, lymph node metastasis, operation method and TNM staging (χ ~ 2 = 4.300-53.315, P <0.05) ). The expression of p-ERK1 / 2 and Cyclin D1 were positively correlated (rs = 0.402,0.742, P <0.001), and there was a positive correlation between the expression of p-ERK1 / 2 and Cyclin D1 = 0.023). Multivariate survival analysis suggested that TROP2 positive expression was an independent risk factor for 3-year survival (relative risk = 2.412, 95% confidence interval: 1.186-5.126, P = 0.010). Conclusion The high expression of TROP2 may play an important role in the malignant progression of gallbladder carcinoma. High expression of TROP2 may mediate the overexpression of p-ERK1 / 2 and Cyclin D1, leading to the malignant progression of gallbladder carcinoma. TROP2 is an independent risk factor for judging the prognosis of patients with gallbladder cancer and may be an effective target for clinical intervention.
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