摘要目的 检测胰腺导管腺癌及相应癌旁胰腺组织TGF-β激活激酶1(TAK1)、磷酸化TAK1(p-TAK1)的表达及肿瘤相关巨噬细胞(TAM)的浸润密度,分析二条途径之间的相关性及其与肿瘤临床病理特征的相关性.方法 应用免疫组化法检测57例胰腺癌及35例相应癌旁正常胰腺组织TAK1、p-TAK1及TAM标志物CD68蛋白的表达,计算TAM浸润密度,采用SPSS18.0软件分析它们之间及其与临床病理特征间的关系,采用多因素Logistic回归分析胰腺癌TNM分期的独立危险因素.结果 胰腺癌组织TAK1、p-TAK1蛋白的阳性表达率分别为42.1％(24/57)和40.4％ (23/57),显著高于癌旁组织的14.3％(5/35)和11.4％(4/35);胰腺癌组织CD68阳性的TAM高密度浸润者占38.6％(22/57),显著高于癌旁组织的8.6％(3/35),差异均有统计学意义(P值均＜0.05).TAK1蛋白表达与胰腺肿瘤的最长径、分化程度、淋巴结转移、远处转移、临床分期显著相关;p-TAK1蛋白表达与肿瘤的分化程度、淋巴结转移、远处转移、临床分期显著相关;TAM浸润密度与肿瘤的分化程度、淋巴结转移、远处转移、临床分期显著相关(P值均＜0.05).胰腺癌组织TAK1、p-TAK1表达水平均与TAM的浸润密度呈正相关(P值均＜0.01).多因素Logistic回归分析显示胰腺癌组织TAM高密度浸润是高等级TNM分期的独立危险因素(P =0.002,OR=129.5,95％ CI 6.2 ～2718.6).结论 TAK1途径及TAM在胰腺癌的发生和发展过程中具有重要作用,并且两种机制可能存在一定的协同作用.

abstractsObjective To investigate the expression of TGF-β activated kinase1 (TAK1),phosphoryted TAK1 (p-TAK1) and the density of tumor associated macrophages (TAM) in human pancreatic carcinoma tissues and pairing adjacent normal pancreatic tissues,and explore their relationship.Methods The expression of TAK1,p-TAK1,CD68 (the marker of tumor associated macrophages) proteins in 57 samples of pancreatic cancer tissues and 35 samples of pairing adjacent normal pancreatic tissues were detected by immunohistochemical method,then the density of TAM was evaluated.The relationship between the protein expression and TAM,and the relationship between them and clinicopathologic parameters were examined using SPSS 18.0 software,and the independent risk factors of TNM staging were analyzed by multivariate logistic regression.Results TAK1 and p-TAK1 were positively expressed in 42.1％ (24/57) and 40.4％ (23/57) pancreatic carcinoma tissues,significantly higher than adjacent normal pancreatic tissues [14.3 ％ (5/35) and 11.4％ (4/35)];the proportion of pancreatic carcinoma tissues with high density TAM was 38.6％ (22/57),higher than that of adjacent pancreatic tissues [8.6％ (3/35)],the differences were statistically significant (P＜0.05).TAK1 expression was positively related to tumor size,tumor differentiation,lymph node metastasis,distant metastasis and clinical staging;p-TAK1 expression was positively related to tumor differentiation,lymph node metastasis,distant metastasis and clinical staging;the density of TAM was positively related tumor differentiation,lymph node metastasis,distant metastasis and clinical staging (all the P values were less than 0.05).The expression of TAK1 and p-TAK1were positively correlated with the density of TAM (P ＜0.001).Multivariate logistic regression analysis showed that high density of TAM was independently associated with advanced clinical staging (P =0.002,OR =129.5,95％ CI 6.2 ～2718.6).Conclusions TAK1 pathway and TAM may play an important role in the pathogenesis and progression of pancreatic cancer,and there may be synergy effect between them.