Self-organizing-map-based molecular signature representing the development of hepatocellular carcinoma
Self-organizing-map-based molecular signature representing the development of hepatocellular carcinoma
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DOI：
10.1016/j.febslet.2004.10.113
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发表时间：
2005-02-14
期刊：
影响因子：
3.5
通讯作者：
Hamamoto, Y
中科院分区：
文献类型：
--
作者：
Iizuka, N;Oka, M;Hamamoto, Y
应用高密度寡核苷酸芯片，综合分析了50例丙型肝炎病毒血清学阳性(高分化(G1)、中分化(G2)、低分化(G3))和11例非肿瘤性肝组织(L1、L0)丙型肝炎病毒感染和未感染的肝细胞癌组织中12600个基因的表达水平。我们用有监督的学习方法搜索转换的判别基因(L0对L1，L1对G1，G1对G2，G2对G3)，然后用判别基因集对样本进行自组织映射(SOM)。SOM将这五个簇按照L0、L1、G1、G2和G3的顺序排列在一条独特的S形曲线上。样本排列再现了肝癌的发育相关特征，如P53异常。显著的是，无静脉侵犯的G2肿瘤更接近G1簇，而大多数有静脉侵犯的G2肿瘤更接近G3簇(经Fisher‘s精确检验，P=0.001)。我们目前的概况数据将作为一个框架，以了解肝细胞癌的发展和去分化之间的关系。(C)2005年欧洲生化学会联合会。爱思唯尔出版，版权所有。
Using high-density oligonucleotide array, we comprehensively analyzed expression levels of 12 600 genes in 50 hepatocellular carcinoma (HCC) samples with positive hepatitis C virus (HCV) serology (well (G1), moderately (G2), and poorly (G3) differentiated tumors) and 11 non-tumorous livers (L1 and L0) with and without HCV infection. We searched for discriminatory genes of transition (L0 vs. L1, L1 vs. G1, G1 vs. G2, G2 vs. G3) with a supervised learning method, and then arranged the samples by self-organizing map (SOM) with the discriminatory gene sets. The SOM arranged the five clusters on a unique sigmoidal curve in the order L0, L1, G1, G2, and G3. The sample arrangement reproduced development-related features of HCC such as p53 abnormality. Strikingly, G2 tumors without venous invasion were located closer to the G1 cluster, and most G2 tumors with venous invasion were located closer to the G3 cluster (P = 0.001 by Fisher's exact test). Our present profiling data will serve as a framework to understand the relation between the development and dedifferentiation of HCC. (C) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.