转化生长因子β1与乙醛脱氢酶1在肝内胆管细胞癌的表达及其临床意义

Expression of TGF-β1 and ALDH1 and Their Clinical Significance in Patients with Intrahepatic Cholangiocarcinoma

摘要: 背景：乙醛脱氢酶1 (ALDH1)可作为多种肿瘤干细胞的标志，而对其来源报道较少。体外研究表明转化生长因子β1( transforming growth factorβ1, TGF-β1)能诱导肿瘤干细胞的产生，而胆管细胞癌组织中TGF-β1表达与ALDH1的关系尚未阐明。方法：采用定量PCR检测7例正常胆管、18例胆管细胞癌新鲜组织中TGF-β1和ALDH1 mRNA的表达，免疫组织化学染色的方法检测58例肝内胆管细胞癌石蜡组织中TGF-β1和ALDH1蛋白的表达。结果：胆管细胞癌组织中TGF-β1的mRNA水平明显高于正常胆管(P = 0.046)，ALDH1的mRNA水平无统计学差异。肝内胆管细胞癌组织中TGF-β1低表达组28例，高表达组30例，高表达阳性率为51.72%，ALDH1低表达组23例，高表达组35例，高表达阳性率为60.34%，TGF-β1与ALDH1的表达呈正相关(r = 0.583, P < 0.001)。肝内胆管癌组织中TGF-β1及ALDH1表达在肿瘤低分化组高于高分化组(P值分别为0.003、0.011)，ALDH1表达在术前血浆CA199浓度高水平组高于低水平组(P = 0.041)。肝内胆管细胞癌组织中TGF-β1及ALDH1高水平组患者的总生存率低于低水平组(P值分别为0.012、0.033)。多因素Cox回归模型分析显示TGF-β1表达量是影响肝内胆管细胞癌患者预后的独立危险因素(P = 0.014)。结论：肝内胆管细胞癌组织中TGF-β1表达与ALDH1表达有关；肝内胆管细胞癌组织中TGF-β1表达量可作为预测患者术后预后的指标。

Abstract: Background: Aldehyde dehydrogenase 1 (ALDH1) has been proved to be the marker of cancer stem cells (CSCs) in different types of tumors. However, the research of its source is rare. Recent studies showed that transforming growth factor β1 (TGF-β1) could induce the generation of CSCs. However, the correlation of TGF-β1 and ALDH1 expression in patients with intrahepatic cholangiocarcinoma (ICC) is unclear. Method: Expression of TGF-β1 and ALDH1 were detected in seven normal bile duct and eighteen cholangiocarcinoma tissues by quantitative PCR. Expression of TGF-β1 and ALDH1 were detected in fifty eight ICC tissues by using immunohistochemistry (IHC) technique. Results: Quantitative PCR showed that the expression of TGF-β1 in cholangiocarcinoma patients was higher than normal bile duct (P = 0.046). Immunohistochemical staining showed that the expression of TGF-β1 was correlated with the expression of ALDH1 in ICC patients (P < 0.001). Both of TGF-β1 and ALDH1 expression were correlated with tumor differentiation (P = 0.003 or P = 0.011) and ALDH1 expression was correlated with the level of CA199 (P = 0.041). Both of TGF-β1 and ALDH1 expression were prognostic factors in ICC patients (P = 0.012 or P = 0.033). Cox multivariate model showed that TGF-β1 expression was independent prognostic factors in ICC patients (P = 0.014). Conclusion: The expression of TGF-β1 is related to the expression of ALDH1 in ICC patients. And the expression of TGF-β1 can be used as the independent predictor for the prognosis of patients with ICC.