Smoking and cancer-related gene expression in bronchial epithelium and non-small-cell lung cancers
Smoking and cancer-related gene expression in bronchial epithelium and non-small-cell lung cancers
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DOI：
10.1002/path.2039
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发表时间：
2006-10-01
影响因子：
7.3
通讯作者：
Dietmaier, W.
中科院分区：
文献类型：
--
作者：
Woenckhaus, M.;Klein-Hitpass, L.;Dietmaier, W.
吸烟是全世界肺癌的主要原因。使用 Affymetrix U133A 阵列研究了手术切除和显微解剖的非小细胞肺癌（18 例鳞状细胞癌和 9 例腺癌）、匹配的正常支气管上皮以及吸烟者 (n = 22) 和非吸烟者 (n = 5) 的外周肺组织样本中的基因表达。通过实时 PCR 或免疫组织化学验证了 15 个差异调节基因的子集。层次聚类分析清楚地区分良性和恶性组织以及鳞状细胞癌和腺癌。支气管上皮癌和腺癌可分为吸烟者和非吸烟者两个亚组。通过比较非吸烟者、吸烟者和匹配的癌症组织的支气管上皮中的基因表达谱，可以识别23个差异表达基因的特征，这可能反映吸烟者中央支气管上皮中早期香烟烟雾诱导的和癌症相关的分子病变。其中 10 个基因涉及外源代谢和氧化还原应激（例如 AKR1B10、AKR1C1 和 MT1K）。一种基因是抑癌基因（HLF）；两个基因作为癌基因（FGFR3 和 LM03）；两个基因参与基质降解（MMP12 和 PTHLH）；三个基因与细胞分化相关（SPRR1B、RTN1 和 MUC7）；迄今为止，有五个基因尚未得到很好的表征。通过将吸烟者暴露于烟草的外周肺泡肺组织与非吸烟者以及吸烟者的腺癌进行比较，可以鉴定出 27 个其他差异表达基因的特征。这些基因参与异生物质（例如GPX2和FM03）的代谢，并且可能代表香烟烟雾诱发的癌症相关分子靶点，可用于识别吸烟者患肺癌风险增加的情况。版权所有 (c) 2006 大不列颠及爱尔兰病理学会。由约翰·威利父子有限公司出版
Tobacco smoking is the leading cause of lung cancer worldwide. Gene expression in surgically resected and microdissected samples of non-small-cell lung cancers (18 squamous cell carcinomas and nine adenocarcinomas), matched normal bronchial epithelium, and peripheral lung tissue from both smokers (n = 22) and non-smokers (n = 5) was studied using the Affymetrix U133A array. A subset of 15 differentially regulated genes was validated by real-time PCR or immunohistochemistry. Hierarchical cluster analysis clearly distinguished between benign and malignant tissue and between squamous cell carcinomas and adenocarcinomas. The bronchial epithelium and adenocarcinomas could be divided into the two subgroups of smokers and non-smokers. By comparison of the gene expression profiles in the bronchial epithelium of non-smokers, smokers, and matched cancer tissues, it was possible to identify a signature of 23 differentially expressed genes, which might reflect early cigarette smoke-induced and cancer-relevant molecular lesions in the central bronchial epithelium of smokers. Ten of these genes are involved in xenobiotic metabolism and redox stress (eg AKR1B10, AKR1C1, and MT1K). One gene is a tumour suppressor gene (HLF); two genes act as oncogenes (FGFR3 and LM03); two genes are involved in matrix degradation (MMP12 and PTHLH); three genes are related to cell differentiation (SPRR1B, RTN1, and MUC7); and five genes have not been well characterized to date. By comparison of the tobacco-exposed peripheral alveolar lung tissue of smokers with non-smokers and with adenocarcinomas from smokers, it was possible to identify a signature of 27 other differentially expressed genes. These genes are involved in the metabolism of xenobiotics (eg GPX2 and FM03) and may represent cigarette smoke-induced, cancer-related molecular targets that may be utilized to identify smokers with increased risk for lung cancer. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.