1. ¹Department of Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka Suita, Osaka 565-0871, Japan
2. ²DNA Chip Research Inc., 1-1-43 Suehirocho, Tsurumi, Yokohama, Kanagawa 230-0045, Japan

Correspondence: Dr I Takemasa, E-mail: itakemasa@gesurg.med.osaka-u.ac.jp

Received 17 April 2008; Revised 18 August 2008; Accepted 28 August 2008; Published online 30 September 2008.

Abstract

Gene expression profiling is a valuable tool for identifying differentially expressed genes in studies of disease subtype and patient outcome for various cancers. However, it remains difficult to assign biological significance to the vast number of genes. There is an increasing awareness of gene expression profile as an important part of the contextual molecular network at play in complex biological processes such as cancer initiation and progression. This study analysed the transcriptional profiles commonly activated at different stages of gastric cancers using an integrated approach combining gene expression profiling of 222 human tissues and gene regulatory dynamic mapping. We focused on an inferred core network with CDKN1A (p21^WAF1/CIP1) as the hub, and extracted seven candidates for gastric carcinogenesis (MMP7, SPARC, SOD2, INHBA, IGFBP7, NEK6, LUM). They were classified into two groups based on the correlation between expression level and stage. The seven genes were commonly activated and their expression levels tended to increase as disease progressed. NEK6 and INHBA are particularly promising candidate genes overexpressed at the protein level, as confirmed by immunohistochemistry and western blotting. This integrated approach could help to identify candidate players in gastric carcinogenesis and progression. These genes are potential markers of gastric cancer regardless of stage.