State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, 651 Dongfeng East Road, Guangzhou, 510060 Guangdong Province, People's Republic of China.
Med Oncol. 2012 Sep;29(3):1843-9. doi: 10.1007/s12032-011-0075-x. Epub 2011 Oct 11.
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.
微阵列数据分析表明，醛脱氢酶 1 家族成员 L1（ALDH1L1）在肝细胞癌（HCC）中的表达降低。然而，ALDH1L1 在 HCC 发生中的作用尚未阐明。在本研究中，我们研究了 ALDH1L1 在 HCC 中的表达，并评估了其与 HCC 患者临床特征和预后的关系。总共收集了 112 例接受根治性肝切除术的 HCC 患者的 112 个肿瘤样本。在 112 个样本中，通过实时定量 RT-PCR（qRT-PCR）和 Western blot 分析了 16 对 HCC 肿瘤组织和相应的相邻非肿瘤组织，并用免疫组织化学方法检测了 96 个 HCC 样本。qRT-PCR 检测结果显示，肿瘤组织中 ALDH1L1 的 mRNA 水平明显低于相邻非肿瘤组织（P = 0.0007），Western blot 分析表明肿瘤组织中 ALDH1L1 的蛋白水平也明显下调。免疫组化检测显示，56.3%（54/96）的 HCC 患者存在 ALDH1L1 表达降低。相关性分析显示，ALDH1L1 表达与组织学分级（P = 0.001）、HBsAg 状态（P = 0.024）和血清 AFP（P = 0.001）显著相关。ALDH1L1 低表达的患者预后较高表达的患者差（P = 0.008）。多变量分析显示，ALDH1L1 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）。本研究首次揭示，ALDH1L1 的 mRNA 和蛋白表达在 HCC 组织中显著降低，其低蛋白表达是 HCC 患者生存的新的潜在预后标志物。
