Discovery of a new biomarker for gastroenterological cancers.

Various genomic technologies have been applied to address crucial problems in cancer biology, because cancer develops through the accumulation of various genetic alterations. Of these, gene expression profiling analysis using microarray technology has been widely applied not only to classify cancers at molecular levels, but also to identify novel molecular targets for therapeutics and/or diagnostics. To gain molecular understanding of gastric carcinogenesis, progression, and diversity, we analyzed primary advanced gastric cancer and noncancerous gastric tissues by high-density oligonucleotide microarray. Genes differentially expressed between cancer and noncancerous tissues were identified. In cancer tissues, genes related to cell cycle, growth factor, cell motility, cell adhesion, and matrix remodeling were highly expressed, whereas those related to gastrointestinal-specific function and immune response were rather downregulated. These results provide not only a new molecular basis for understanding biological properties of gastric cancer but also useful resources for future development of therapeutic and diagnostic biomarkers for gastric cancer. Several microarray studies have been published since and have been compared for validation in meta-analysis. As integration of transcriptome information with other biological data is crucial to interpret gene expression data, we have applied oligonucleotide microarray technology to assess allelic gene dosage at 10000 polymorphic loci, namely with an average interval of 200kb. Using a newly developed algorithm, genome imbalance map, loss of heterozygosity (LOH) status can be determined simultaneously. Besides several loci with genomic amplification, we also identified a homozygously deleted chromosomal region in 7q, where frequent chromosomal instability was observed. Finally, we are currently developing novel biomarkers for gastroenterological cancers. Glypican 3 is detected at high levels in serum of hepatocellular carcinoma patients and could be a potential target for antibody therapy.