摘要目的 研究胆囊癌组织中趋化因子受体CCR4的表达,以及CCR4与临床病理因素的相互关系及其对胆囊癌预后的影响.方法 免疫组织化学法检测CCR4在胆囊癌组织标本及慢性胆囊炎胆囊黏膜组织标本中的表达情况,结合临床资料进行分析.Kaplan-Meier法进行CCR4表达阳性组与阴性组生存曲线比较.Cox回归模型进行多因素分析.x2检验分析CCR4在胆囊癌组织中的表达与临床病理因素的相关性.结果 胆囊癌细胞胞浆和(或)胞膜有CCR4表达,呈棕黄色.胆囊癌CCR4蛋白的表达明显高于慢性胆囊炎胆囊上皮组织(P＜0.05).CCR4的高表达与胆囊癌患者的性别、年龄、病理分级、远处转移及神经淋巴管侵犯等因素无关,而与肿瘤淋巴结转移(P＜0.05)及组织学分级有关(P＜0.05).Kaplan Meier生存分析结果显示CCR4阳性组与阴性组术后生存时间差异有统计学意义(P＜0.05).多因素分析表明,CCR4表达水平是影响胆囊癌患者手术后生存的独立危险因素.结论 趋化因子受体CCR4在胆囊癌组织中有表达,且与肿瘤淋巴结转移及组织学分级有关,是胆囊癌患者术后生存的独立危险因素;趋化因子受体CCR4与胆囊癌的侵袭与转移有关.基于CCR4的抗肿瘤靶点技术有望成为治疗胆囊癌的一种新方式.

abstractsObjective To study the expression of CCR4 in gallbladder carcinoma tissues,and to determine its relationship with clinical pathological factors and its influence on prognosis of gallbladder cancer.Methods The expressions of CCR4 in gallbladder carcinoma tissues,and chronic cholecystitis gallbladder mucosal tissues were detected using immune histochemical methods and they were analyzed together with the clinical records.Survival analysis was used to compare the expressions of CCR4 between the positive group and the negative group.Multiple factors analysis was carried out using the Cox regression model.Correlation between the expressions of CCR4 in gallbladder tissues and the clinical pathologic factors was done using the Chi-square test.Results CCR4 is expressed tan-yellow in gallbladder cell cytoplasm and/or cell membrane.The expression of CCR4 protein in the gallbladder carcinoma was obviously higher than in the chronic cholecystitis gallbladder epithelial tissues (P ＜ 0.05).A high expression of CCR4 was not correlated with patients' age,gender,pathological classification,distant metastasis and nerve/lymphatic invasion factors.It was,however correlated with tumor lymph node metastasis (P ＜ 0.05) and histological grading (P ＜ 0.05).Kaplan Meier survival analysis showed the postoperative survival between the CCR4 positive group and the negative group were significant different (P ＜0.05).On multiple factors analysis,CCR4 expression level was an independent risk factor of survival of patients after gallbladder surgery.Conclusions The chemokine receptor CCR4 expressed in gallbladder carcinoma.Its level of expression correlated with lymph node metastasis and histological grading.It was an independent risk factor of survival in patients with gallbladder carcinoma after surgery.As it was associated with invasion and metastasis of gallbladder carcinoma,antitumor treatment targeting CCR4 is expected to become a novel treatment of gallbladder carcinoma.