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    • 1. 发明申请
    • Molecular Characteristics of Non-Small Cell Lung Cancer
    • 非小细胞肺癌的分子特征
    • US20090270265A1
    • 2009-10-29
    • US11829483
    • 2007-07-27
    • Mariana NACHTTatiana DrachevaDavid SidranskyStephen MaddenJin Jen
    • Mariana NACHTTatiana DrachevaDavid SidranskyStephen MaddenJin Jen
    • C40B30/04C12Q1/68C12Q1/26C12Q1/02
    • C12Q1/6886C12Q2600/112C12Q2600/158
    • We used hierarchical clustering to examine gene expression profiles generated by serial analysis of gene expression (SAGE) in a total of nine normal lung epithelial cells and non-small cell lung cancers (NSCLC). Separation of normal and tumor samples, as well as histopathological subtypes, was evident using the 3,921 most abundant transcript tags. This distinction remained when just 115 highly differentially expressed transcript tags were used. Furthermore, these 115 transcript tags clustered into groups that were suggestive of the unique biological and pathological features of the different tissues examined. Adenocarcinomas were characterized by high-level expression of small airway-associated or immunologically related proteins, while squamous cell carcinomas overexpressed genes involved in cellular detoxification or antioxidation. The messages of two p53-regulated genes, p21WAF1/CIP1 and 14-3-3α, were consistently under-expressed in the adenocarcinomas, suggesting that the p53 pathway itself might be compromised in this cancer type. Gene expression observed by SAGE were consistent with the results obtained by quantitative real-time PCR or cDNA array analyses using 43 additional lung tumor and normal samples. Thus, although derived from only a few tissue libraries, molecular signatures of non-small cell lung cancer derived from SAGE most likely represent an unbiased yet distinctive molecular signature for human lung cancer.
    • 我们使用层次聚类来检查在总共九个正常肺上皮细胞和非小细胞肺癌(NSCLC)中通过基因表达(SAGE)的连续分析产生的基因表达谱。 正常和肿瘤样本的分离以及组织病理学亚型,使用3,921个最丰富的转录标签是明显的。 当仅使用115种高度差异表达的转录标记时,这种区别仍然存在。 此外,这115个转录标签聚集成组,提示所检测的不同组织的独特的生物学和病理学特征。 腺癌的特征在于高水平表达小气道相关或免疫相关蛋白,而鳞状细胞癌过表达涉及细胞解毒或抗氧化的基因。 两个p53调控基因p21WAF1 / CIP1和14-3-3alpha的信息在腺癌中一直低表达,表明p53途径本身可能在这种癌症类型中受损。 通过SAGE观察到的基因表达与通过使用43个额外的肺肿瘤和正常样品的定量实时PCR或cDNA阵列分析获得的结果一致。 因此,尽管仅来自少数组织文库,但从SAGE衍生的非小细胞肺癌的分子特征最可能代表人类肺癌的无偏差但独特的分子特征。