Decreased expression of ALDH1L1 is associated with a poor prognosis in hepatocellular carcinoma
Decreased expression of ALDH1L1 is associated with a poor prognosis in hepatocellular carcinoma
复制标题
DOI：
10.1007/s12032-011-0075-x
复制
发表时间：
2012-09-01
期刊：
影响因子：
3.4
通讯作者：
Wang, Hui-Yun
中科院分区：
文献类型：
--
作者：
Chen, Xiao-Qian;He, Juan-Ru;Wang, Hui-Yun
芯片数据表明，醛脱氢酶1家族成员L1（ALDH 1 L1）的表达在肝细胞癌（HCC）中减少。然而，ALDH 1 L1在HCC发生中的作用尚未阐明。本研究旨在探讨ALDH 1 L1在HCC中的表达及其与HCC患者临床特征和预后的关系。共收集了112例接受根治性肝切除术的HCC患者的肿瘤样本。对112例肝癌组织中16例癌组织和相应癌旁组织进行实时荧光定量RT-PCR（qRT-PCR）和Western blotting检测，对96例肝癌组织进行免疫组化检测。qRT-PCR结果显示，ALDH 1 L1在肿瘤组织中的mRNA水平显著低于癌旁组织（P = 0.0007），蛋白质印迹结果显示ALDH 1 L1在肿瘤组织中的蛋白水平也显著下调。免疫组化检测显示，56.3%（54/96）的HCC患者ALDH 1 L1表达降低。相关分析显示ALDH 1 L1表达与组织分化程度（P = 0.001）、HBsAg状态（P = 0.024）和血清AFP（P = 0.001）显著相关。ALDH 1 L1低表达组患者预后差于高表达组（P = 0.008）。多因素分析显示ALDH 1 L1表达是总生存期的独立预测因子（HR，0.349; 95%CI，0.157-0.774; P = 0.01）。本研究的结果首次揭示了ALDH 1 L1的mRNA和蛋白表达在HCC组织中显著降低，其低蛋白表达是HCC患者生存的一个新的和潜在的预后标志。
Microarray data suggested that the expression of aldehyde dehydrogenase 1 family member L1 (ALDH1L1) is reduced in hepatocellular carcinoma (HCC). However, the role of ALDH1L1 in HCC carcinogenesis has not been elucidated. In the present study, we investigated the expression of ALDH1L1 in HCC and evaluated its relationship with clinical features and prognosis of HCC patients. Total 112 tumor samples were collected from patients with HCC, who underwent radical hepatectomy. Out of the 112 samples, 16 paired HCC tumorous and corresponding adjacent nontumor tissues were analyzed by real-time quantitative RT-PCR (qRT-PCR) and Western blotting, and the other 96 HCC samples were detected by immunohistochemical method. The qRT-PCR assay showed that the mRNA level of ALDH1L1 was significantly reduced in tumorous tissues compared with the adjacent nontumorous tissues (P = 0.0007), and Western blotting indicated that protein level of ALDH1L1 also notably down-regulated in tumor tissues. Immunohistochemistry detection revealed that decreased ALDH1L1 expression was present in 56.3% (54/96) of HCC patients. Correlation analysis showed that ALDH1L1 expression was significantly correlated with histological differentiation (P = 0.001), HBsAg status (P = 0.024) and serum AFP (P = 0.001). Patients with low expression of ALDH1L1 had poorer prognosis than those with high expression (P = 0.008). Multivariate analysis showed that ALDH1L1 expression was an independent predictor of overall survival (HR, 0.349; 95% CI, 0.157-0.774; P = 0.01). The results in this study, for the first time, reveal that the mRNA and protein expressions of ALDH1L1 are significantly reduced in HCC tissues and its low protein expression is a new and potential prognostic marker for the survival of HCC patients.