ALDH1A1和ALDH6A1在肝门部胆管癌中的表达及其临床意义

Expression of ALDH1A1 and ALDH6A1 in hilar cholangiocarcinoma and their clinical significance

目的探讨乙醛脱氢酶1A1(ALDH1A1)和乙醛脱氢酶6A1(ALDH6A1)在肝门部胆管癌组织中的表达及临床意义。方法收集东方肝胆外科医院2005年至2007年手术切除的49例肝门部胆管癌组织和10例配对的癌旁组织。采用免疫组化SP法检测上述组织中ALDH1A1和ALDH6A1的表达情况,分析两者表达与患者临床病理特征和预后的关系。结果在49例癌组织中,ALDH1A1和ALDH6A1蛋白的高表达率分别为69.4%(34/49)和44.9%(22/49),明显高于癌旁组织的30.0%(3/10)和10.0%(1/10)。ALDH1A1和ALDH6A1的表达与淋巴结转移有关(P<0.05),而与性别、年龄、TNM分期、肿瘤大小、浸润深度和神经侵犯无关(P>0.05)。ALDH1A1高表达者的中位无进展生存期(PFS)和中位总生存期(OS)均为12个月,明显短于低表达者的32个月和42个月,差异有统计学意义(P<0.05)。ALDH6A1高表达者的中位OS为16个月,短于低表达者的23个月,差异有统计学意义(P<0.05);ALDH6A1高表达者的中位PFS为15个月,短于低表达者的22个月,但差异无统计学意义(P>0.05)。Cox多因素分析显示,浸润深度和淋巴结转移是影响PFS的独立因素(P<0.05),浸润深度、淋巴结转移和ALDH1A1表达是影响OS的独立因素(P<0.05)。结论 ALDH1A1和ALDH6A1在肝门部胆管癌组织中表达增强,与肝门部胆管癌的发生、发展有关,ALDH1A1是评估预后潜在的肿瘤标志物。

Objective To investigate the expression of aldehyde dehydrogenase 1A1（ALDH1A1） and aldehyde dehydrogenase 6A1（ALDH6A1） in hilar cholangiocarcinoma tissues and their clinical significance.Methods Forty-nine cases of hilar cholangiocarcinoma tissues and 10 cases of tumor-adjacent tissues were enrolled from 2005 to 2007.The expression of ALDH1A1 and ALDH6A1 was detected by immunohistochemical SP staining.The correlation of their expression and clinicopathological features as well as prognosis was evaluated.Results The high expression rates of ALDH1A1 and ALDH6A1 were 69.4%（34/49） and 44.9%（22/49）,higher than 30.0%（3/10） and 10.0%（1/10） in tumor-adjacent tissues respectively（P 0.05）.The expression of ALDH1A1 and ALDH6A1 were related to lymph node metastasis（P 0.05）,but not to gender,age,TNM staging,tumor size,the depth of tumor invasion and nervous invasion（P 0.05）.The median progression-free survival（PFS） and median overall survival（OS） of ALDH1A1-high expression patients were shorter than those of ALDH1A1-low expression patients（12 months vs.32 months,12 months vs.42 months,both P 0.05）.The median OS of ALDH6A1-high expression patients was shorter than that of ALDH6A1-low expression patients（16 months vs.23 months,P 0.05）,whereas there was no significant difference between median PFS of ALDH6A1-high expression and ALDH6A1-low expression patients（15 months vs.22 months,P 0.05）.Cox multivariate analysis revealed that the depth of invasion and lymph node metastasis were independent factors influencing PFS,and the depth of invasion,lymph node metastasis and ALDH1A1 expression were independent factors influencing OS.Conclusion ALDH1A1 and ALDH6A1 were significantly up-regulated in hilar cholangiocarcinoma tissues,and their expression is associated with the development of hilar cholangiocarcinoma.ALDH1A1 may be a new biomarker for predicting the prognosis of hilar cholangiocarcinoma.