Two subclasses of lung squamous cell carcinoma with different gene expression profiles and prognosis identified by hierarchical clustering and non-negative matrix factorization
Two subclasses of lung squamous cell carcinoma with different gene expression profiles and prognosis identified by hierarchical clustering and non-negative matrix factorization
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DOI：
10.1038/sj.onc.1208858
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发表时间：
2005-10-27
期刊：
影响因子：
8
通讯作者：
Ishikawa, Y
中科院分区：
文献类型：
--
作者：
Inamura, K;Fujiwara, T;Ishikawa, Y
目前用于定义肺鳞状细胞癌（SCC）的临床和组织病理学标准不足以预测临床结果。为了通过基因表达谱进行临床有用的分类，我们使用40 386个元件的cDNA微阵列分析了48个SCC，9个腺癌和30个正常肺样本。通过分层聚类（HC）的初步分析允许将SCC分为两个不同的亚类。一个额外的独立轮HC诱导一个类似的分区和共识聚类与非负矩阵分解方法表明这种分类的鲁棒性。Kaplan-Meier分析和对数秩检验表明，两组的生存率无显著差异（P = 0.071），但两组6年生存率的可能性有显著差异（40.5% vs 81.8%，P = 0.014，Z检验）。统计学上确定了每个亚类的生物过程特征类别，并且在预后不良的亚类中细胞增殖相关基因的上调是明显的。在具有更好存活率的亚类中，参与分化的细胞内功能的基因，例如MAPKKK级联、神经酰胺代谢或转录调节，被上调。这项工作代表了重要的一步，确定临床有用的分类肺SCC。
Current clinical and histopathological criteria used to define lung squamous cell carcinomas (SCCs) are insufficient to predict clinical outcome. To make a clinically useful classification by gene expression profiling, we used a 40 386 element cDNA microarray to analyse 48 SCC, nine adenocarcinoma, and 30 normal lung samples. Initial analysis by hierarchical clustering (HC) allowed division of SCCs into two distinct subclasses. An additional independent round of HC induced a similar partition and consensus clustering with the non-negative matrix factorization approach indicated the robustness of this classification. Kaplan-Meier analysis with the log-rank test pointed to a nonsignificant difference in survival (P = 0.071), but the likelihood of survival to 6 years was significantly different between the two groups (40.5 vs 81.8%, P = 0.014, Z-test). Biological process categories characteristic for each subclass were identified statistically and upregulation of cell-proliferation-related genes was evident in the subclass with poor prognosis. In the subclass with better survival, genes involved in differentiated intracellular functions, such as the MAPKKK cascade, ceramide metabolism, or regulation of transcription, were upregulated. This work represents an important step toward the identification of clinically useful classification for lung SCC.