Molecular classification of nodal metastasis in primary larynx squamous cell carcinoma

Molecular classification of nodal metastasis in primary larynx squamous cell carcinoma
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DOI:
10.1016/j.trsl.2007.03.011
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发表时间:
2007-10-01
影响因子:
7.8
通讯作者:
Tete, Stefano
Tete, Stefano
中科院分区:
医学2区
文献类型:
--
作者:
Carinci, Francesco;Arcelli, Diego;Tete, Stefano

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喉鳞状细胞癌(LSCC)的分类和预后取决于临床和组织病理学检查。目前,表达谱具有调查、分类和更好地管理癌症的潜力。用包含19,200个cDNA的微阵列分析了22个原代喉癌的基因表达谱。Goal对差异表达的基因进行了功能分类,并通过一种新的“硅胶”程序确定了差异转录的物理基因簇。158个分化肿瘤有淋巴结转移的基因特征。一种新的统计方法允许将转移性肿瘤分类为两个不同的亚组差异基因表达模式。在与淋巴结转移相关的基因中,我们在体外证实了NM23-H3降低了细胞的活力,而TRIM8是一种生长抑制因子。6个染色体区域在转移性肿瘤中特异性下调。这种大规模的喉癌基因表达分析提供了与淋巴结转移相关的基因组活性变化的信息,并确定了可能被证明是有用的新治疗靶点的分子。
Classification and prognosis of larynx squamous cell carcinoma (LSCC) depends on clinical and histopathological examination. Currently, expression profiling harbors the potential to investigate, classify, and better manage cancer. Gene expression profiles of 22 primary LSCCs were analyzed by microarrays containing 19,200 cDNAs. GOAL functionally classified differentially expressed genes, and a novel "in silica" procedure identified physical gene clusters differentially transcribed. A signature of 158 genes differentiated tumors with nodal metastasis. A novel statistical method allowed categorization of metastatic tumors into 2 distinct subgroups of differential gene expression patterns. Among genes correlated to nodal metastatic progression, we verified in vitro that NM23-H3 reduced cell motility and TRIM8 were a growth suppressor. Six chromosomal regions were specifically downregulated in metastatic tumors. This large-scale gene expression analysis in LSCC provides information on changes in genomic activity associated with lymphonodal metastasis and identifies molecules that might prove useful as novel therapeutic targets.