Abstract
Gastric cancer is the fourth leading cause of cancer-related death in the world. Two histologically distinct types of gastric carcinoma, ‘intestinal’ and ‘diffuse’, have different epidemiological and pathophysiological features that suggest different mechanisms of carcinogenesis. A number of studies have investigated intestinal-type gastric cancers at the molecular level, but little is known about mechanisms involved in the diffuse type, which has a more invasive phenotype and poorer prognosis. To clarify the mechanisms that underlie its development and/or progression, we compared the expression profiles of 20 laser-microbeam-microdissected diffuse-type gastric-cancer tissues with corresponding noncancerous mucosae by means of a cDNA microarray containing 23 040 genes. We identified 153 genes that were commonly upregulated and more than 1500 that were commonly downregulated in the tumors. We also identified a number of genes related to tumor progression. Furthermore, comparison of the expression profiles of diffuse-type with those of intestinal-type gastric cancers identified 46 genes that may represent distinct molecular signatures of each histological type. The putative signature of diffuse-type cancer exhibited altered expression of genes related to cell–matrix interaction and extracellular-matrix (ECM) components, whereas that of intestinal-type cancer represented enhancement of cell growth. These data provide insight into different mechanisms underlying gastric carcinogenesis and may also serve as a starting point for identifying novel diagnostic markers and/or therapeutic targets for diffuse-type gastric cancers.
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Acknowledgements
We thank Ms Tae Makino for technical assistance, Ms Emi Ichihashi for data analysis, Dr Naoki Oyaizu for reviewing the pathological data of samples, Dr Arimichi Takabayashi, Dr Koichi Matsuo, Dr Akira Togashi, Dr Kazutaka Obama, Dr Takefumi Kikuchi, Dr Toshihiko Nishidate and Dr Soji Kakiuchi for helpful discussions and Dr Meiko Takahashi for preparation of the manuscript. This work was supported in part by Research for the Future Program Grant (00L01402) from the Japan Society for the Promotion of Science.
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Jinawath, N., Furukawa, Y., Hasegawa, S. et al. Comparison of gene-expression profiles between diffuse- and intestinal-type gastric cancers using a genome-wide cDNA microarray. Oncogene 23, 6830–6844 (2004). https://doi.org/10.1038/sj.onc.1207886
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DOI: https://doi.org/10.1038/sj.onc.1207886
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