Overexpression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers' non-small cell lung carcinomas
Overexpression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers' non-small cell lung carcinomas
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DOI：
10.1158/1078-0432.ccr-04-1238
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发表时间：
2005-03-01
影响因子：
11.5
通讯作者：
Aburatani, H
中科院分区：
文献类型：
--
作者：
Fukumoto, S;Yamauchi, N;Aburatani, H
目的：尽管在组织学和流行病学上存在明显差异，但肺鳞状细胞癌（SCC）和腺癌目前采用相似的治疗方案。本研究的目的是确定一个具有诊断和治疗价值的SCC的分子靶点。实验设计：通过对5个SCC，5个腺癌，10个小细胞肺癌，27个正常组织和40个癌细胞系的微阵列分析，探索SCC中特异性上调的基因。结果：筛选出醛酮还原酶家族1成员B10（AKR1B10）等7个SCC特异性基因。应用免疫组化方法检测101例非小细胞肺癌（NSCLC）组织中AKR1B10的表达，发现32例SCC中有27例（84.4%）表达AKR1B10，65例腺癌中有19例（29.2%）表达AKR1B10。多元回归分析显示吸烟是非小细胞肺癌和腺癌中AKR1B10表达的独立变量（P <0.01）。结论：AKR1B10在绝大多数SCC中呈高表达，且与吸烟密切相关，在吸烟者的腺癌中也有较高表达。这些结果表明，AKR1B10是一个潜在的诊断标记物，特异性吸烟者的NSCLC，并可能参与烟草相关的致癌作用。
Purpose: Squamous cell carcinoma (SCC) and adenocarcinoma of the lung are currently subject to similar treatment regimens despite distinct differences in histology and epidemiology. The aim of this study is to identify a molecular target with diagnostic and therapeutic values for SCC.Experimental Design: Genes specifically up-regulated in SCC were explored through microarray analysis of 5 SCCs, 5 adenocarcinomas, 10 small cell lung carcinomas, 27 normal tissues, and 40 cancer cell lines. Clinical usefulness of these genes was subsequently examined mainly by immunohistochemical analysis.Results: Seven genes, including aldo-keto, reductase family 1, member B10 (AKR1B10), were identified as SCC-specific genes. AKR1B10 was further examined by immunohistochemical analysis of 101 non-small cell lung carcinomas (NSCLC) and its overexpression was observed in 27 of 32 (84.4%) SCCs and 19 of 65 (29.2%) adenocarcinomas. Multiple regression analysis showed that smoking was an independent variable responsible for AKR1B10 overexpression in NSCLCs (P < 0.01) and adenocarcinomas (P < 0.01). AKR1B10 staining was occasionally observed even in squamous metaplasia, a precancerous lesion of SCC.Conclusion: AKR1B10 was overexpressed in most cases with SCC, which is closely associated with smoking, and many adenocarcinoma cases of smokers. These results suggest that AKR1B10 is a potential diagnostic marker specific to smokers' NSCLCs and might be involved in tobacco-related carcinogenesis.