Low expression of aldehyde dehydrogenase 1A1 (ALDH1A1) is a prognostic marker for poor survival in pancreatic cancer.
Low expression of aldehyde dehydrogenase 1A1 (ALDH1A1) is a prognostic marker for poor survival in pancreatic cancer.
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DOI：
10.1186/1471-2407-11-275
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发表时间：
2011-06-27
期刊：
影响因子：
3.8
通讯作者：
Weitz J
中科院分区：
文献类型：
--
作者：
Kahlert C;Bergmann F;Beck J;Welsch T;Mogler C;Herpel E;Dutta S;Niemietz T;Koch M;Weitz J
乙醛脱氢酶1（ALDH 1）已被表征为不同类型肿瘤中的癌症干细胞标志物。此外，它在基因调控中起着关键作用，并赋予肿瘤细胞增强的化疗抗性。最近，ALDH 1A 1已被描述为胰腺癌组织微阵列中的预后标志物。本研究的目的是重新评估ALDH 1A 1的表达作为一个预后标志物的整体安装组织切片。采用实时定量PCR（qRT-PCR）和蛋白质印迹法评估ALDH 1A 1在7种胰腺癌细胞系和1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标本进行ALDH 1A 1和Ki-67免疫染色。免疫组化结果与组织病理学和临床资料相关。qRT-PCR和Western blotting显示ALDH 1A 1在不同恶性和非恶性胰腺细胞系中的表达模式不同。免疫组化结果显示，ALDH 1A 1仅在72例（74%）患者的细胞质中表达，而25例（26%）患者为阴性。ALDH 1A 1的高表达与增殖率的增加显著相关（斯皮尔曼相关性，p = 0.01）。单因素和多因素分析显示ALDH 1A 1表达降低是影响总生存率的独立不良预后因素。免疫组织化学分析显示，ALDH 1A 1在胰腺癌中的表达比最初通过组织微阵列分析报道的要丰富。此外，ALDH 1A 1的高表达与肿瘤细胞的增殖显著相关。有趣的是，这项研究是第一个将ALDH 1A 1的低表达确定为胰腺癌总生存率的独立不良预后标志物。
Aldehyde deyhdrogenase 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. 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. 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. Immunonhistochemical 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.
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影响因子：
11.2
作者：
Huang EH;Hynes MJ;Zhang T;Ginestier C;Dontu G;Appelman H;Fields JZ;Wicha MS;Boman BM
通讯作者：
Boman BM
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Simeone, Diane M.