Kittaka Nobuyoshi, Takemasa Ichiro, Takeda Yutaka, Marubashi Shigeru, Nagano Hiroaki, Umeshita Koji, Dono Keizo, Matsubara Kenichi, Matsuura Nariaki, Monden Morito
Department of Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Eur J Cancer. 2008 Apr;44(6):885-97. doi: 10.1016/j.ejca.2008.02.019. Epub 2008 Mar 11.
DNA microarray analysis of human cancer has resulted in considerable accumulation of global gene profiles. However, extraction and understanding the underlying biology of cancer progression remains a significant challenge. This study applied a novel integrative computational and analytical approach to this challenge in human hepatocellular carcinoma (HCC) with the aim of identifying potential molecular markers or novel therapeutic targets. We analysed 100 HCC tissue samples by human 30K DNA microarray. The gene expression data were uploaded into the network analysis tool, and the biological networks were displayed graphically. We identified several activated 'hotspot' regions harbouring a concentration of upregulated genes. Several 'hotspot' regions revealed integrin and Akt/NF-kappaB signalling. We identified key members linked to these signalling pathways including osteopontin (SPP1), glypican-3 (GPC3), annexin 2 (ANXA2), S100A10 and vimentin (VIM). Our integrative approach should significantly enhance the power of microarray data in identifying novel potential targets in human cancer.
对人类癌症的DNA微阵列分析已带来了大量全球基因图谱的积累。然而，提取并理解癌症进展的潜在生物学机制仍然是一项重大挑战。本研究针对人类肝细胞癌（HCC）的这一挑战应用了一种新颖的综合计算与分析方法，旨在识别潜在的分子标志物或新型治疗靶点。我们通过人类30K DNA微阵列分析了100份HCC组织样本。将基因表达数据上传至网络分析工具，并以图形方式展示生物网络。我们识别出了几个激活的“热点”区域，这些区域含有集中的上调基因。几个“热点”区域显示整合素和Akt/NF-κB信号传导。我们识别出了与这些信号通路相关的关键成员，包括骨桥蛋白（SPP1）、磷脂酰肌醇蛋白聚糖-3（GPC3）、膜联蛋白2（ANXA2）、S100A10和波形蛋白（VIM）。我们的综合方法应能显著增强微阵列数据在识别人类癌症新型潜在靶点方面的能力。
