醛脱氢酶 1A1（ALDH1A1）低表达是胰腺癌预后不良的标志。
Low expression of aldehyde dehydrogenase 1A1 (ALDH1A1) is a prognostic marker for poor survival in pancreatic cancer.
机构信息
Department of General, Visceral and Transplantation Surgery, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
出版信息
BMC Cancer. 2011 Jun 27;11:275. doi: 10.1186/1471-2407-11-275.
BACKGROUND
Aldehyde dehydrogenase 1 (ALDH1) has been characterised as a cancer stem cell marker in different types of tumours. Additionally, it plays a pivotal role in gene regulation and endows tumour cells with augmented chemoresistance. Recently, ALDH1A1 has been described as a prognostic marker in a pancreatic cancer tissue microarray. The aim of this study was to reevaluate the expression of ALDH1A1 as a prognostic marker on whole-mount tissue sections.
METHODS
Real-time-quantitative-PCR (qRT-PCR) and Western blotting were used to evaluate the expression profile of ALDH1A1 in seven pancreatic cancer cell lines and one non-malignant pancreatic cell line. Immunostaining against ALDH1A1 and Ki-67 was performed on paraffin-embedded samples from 97 patients with pancreatic cancer. The immunohistochemical results were correlated to histopathological and clinical data.
RESULTS
qRT-PCR and Western blotting revealed a different expression pattern of ALDH1A1 in different malignant and non-malignant pancreatic cell lines. Immunohistochemical analysis demonstrated that ALDH1A1 was confined to the cellular cytoplasm and occurred in 72 cases (74%), whereas it was negative in 25 cases (26%). High expression of ALDH1A1 was significantly correlated to an increased proliferation rate (Spearman correlation, p = 0.01). Univariate and multivariate analyses showed that decreased expression of ALDH1A1 is an independent adverse prognostic factor for overall survival.
CONCLUSIONS
Immunohistochemical analysis on whole-mount tissue slides revealed that ALDH1A1 is more abundantly expressed in pancreatic cancer than initially reported by a tissue microarray analysis. Moreover, high expression of ALDH1A1 correlated significantly with the proliferation of tumour cells. Intriguingly, this study is the first which identifies low expression of ALDH1A1 as an independent adverse prognostic marker for overall survival in pancreatic cancer.
背景
醛脱氢酶 1（ALDH1）已被确定为不同类型肿瘤的癌症干细胞标志物。此外，它在基因调控中发挥着关键作用，并赋予肿瘤细胞增强的化疗耐药性。最近，ALDH1A1 已被描述为胰腺癌组织微阵列中的预后标志物。本研究旨在重新评估 ALDH1A1 作为整体组织切片中预后标志物的表达。
方法
使用实时定量 PCR（qRT-PCR）和 Western blot 评估 ALDH1A1 在七种胰腺癌细胞系和一种非恶性胰腺细胞系中的表达谱。对 97 例胰腺癌患者的石蜡包埋样本进行针对 ALDH1A1 和 Ki-67 的免疫染色。将免疫组织化学结果与组织病理学和临床数据相关联。
结果
qRT-PCR 和 Western blot 显示不同恶性和非恶性胰腺细胞系中 ALDH1A1 的表达模式不同。免疫组织化学分析表明，ALDH1A1 局限于细胞细胞质，72 例（74％）中阳性，25 例（26％）中阴性。ALDH1A1 的高表达与增殖率增加显著相关（Spearman 相关性，p = 0.01）。单因素和多因素分析表明，ALDH1A1 表达降低是总生存的独立不良预后因素。
结论
整体组织切片的免疫组织化学分析显示，ALDH1A1 在胰腺癌中的表达比组织微阵列分析最初报道的更为丰富。此外，ALDH1A1 的高表达与肿瘤细胞的增殖显著相关。有趣的是，本研究首次确定 ALDH1A1 表达降低是胰腺癌总生存的独立不良预后标志物。
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