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肺癌中醛脱氢酶1A1(ALDH1A1)和醛脱氢酶3A1(ALDH3A1)的表达:与组织学类型及潜在前体的相关性

ALDH1A1 and ALDH3A1 expression in lung cancers: correlation with histologic type and potential precursors.

作者信息

Patel Miten, Lu Li, Zander Dani S, Sreerama Lakshmaiah, Coco Dominique, Moreb Jan S

机构信息

Department of Medicine, University of Florida, FL, USA.

出版信息

Lung Cancer. 2008 Mar;59(3):340-9. doi: 10.1016/j.lungcan.2007.08.033. Epub 2007 Oct 24.

Abstract

We hypothesize that aldehyde dehydrogenase (ALDH) isozymes may be upregulated in lung tissue as a result of exposure to carcinogenic aldehydes found in cigarette smoke. To investigate this hypothesis, we studied the expression of two ALDH isozymes in lung cancer from patient samples and its relationship to the history of cigarette smoking. Immunohistochemical staining for ALDH1A1 and ALDH3A1 was performed on archival specimens from control patients without lung cancer, and patients with one of the primary lung cancers: squamous cell cancer (SCCA), adenocarcinoma (AdenoCA), and small cell lung cancer (SCLC). An overall score was obtained for each sample based upon multiplying the staining intensity (0-3) and the extensiveness (0-100%). Mean+/-S.E.M. for each experimental group was calculated and compared. Our results indicate a significantly higher level of expression of ALDH1A1 and ALDH3A1 in SCCA (155+/-19 and 162+/-17, respectively) and AdenoCA (116+/-12 and 107+/-10) than SCLC (39+/-11 and 42+/-12) (P<0.01). Atypical pneumocytes demonstrated significantly higher levels of expression of ALDH1A1 and ALDH3A1 than normal pneumocytes (a normal counterpart of AdenoCA), which is suggestive of up regulation during malignant transformation to AdenoCA. A subset analysis of all samples studied revealed increased expression of ALDH1A1 (P=0.055) and ALDH3A1 (P=0.0093) in normal pneumocytes of smokers (n=32) in comparison to those of non-smokers (n=17). Non-small cell lung cancer (NSCLC) express very high levels of ALDH1A1 and ALDH3A1 in comparison with SCLC, elevated expression of both enzymes may be associated with malignant transformation to AdenoCA, and cigarette smoking seems to result in increased expression of these enzymes in normal pneumocytes.

摘要

我们推测,由于接触香烟烟雾中发现的致癌醛类物质,肺组织中的醛脱氢酶(ALDH)同工酶可能会上调。为了验证这一推测,我们研究了患者样本中两种ALDH同工酶在肺癌中的表达情况及其与吸烟史的关系。对无肺癌的对照患者以及患有以下原发性肺癌之一的患者的存档标本进行了ALDH1A1和ALDH3A1的免疫组织化学染色:鳞状细胞癌(SCCA)、腺癌(AdenoCA)和小细胞肺癌(SCLC)。根据染色强度(0 - 3)和广泛程度(0 - 100%)相乘得出每个样本的总分。计算并比较了每个实验组的平均值±标准误。我们的结果表明,SCCA(分别为155±19和162±17)和AdenoCA(116±12和107±10)中ALDH1A1和ALDH3A1的表达水平显著高于SCLC(39±11和42±12)(P<0.01)。非典型肺细胞中ALDH1A1和ALDH3A1的表达水平显著高于正常肺细胞(AdenoCA的正常对应细胞),这表明在向AdenoCA的恶性转化过程中存在上调现象。对所有研究样本的亚组分析显示,与非吸烟者(n = 17)相比,吸烟者(n = 32)的正常肺细胞中ALDH1A1(P = 0.055)和ALDH3A1(P = 0.0093)的表达增加。与SCLC相比,非小细胞肺癌(NSCLC)中ALDH1A1和ALDH3A1的表达水平非常高,这两种酶的表达升高可能与向AdenoCA的恶性转化有关,吸烟似乎会导致正常肺细胞中这些酶的表达增加。

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