Transcriptome dissection of gastric cancer: identification of novel diagnostic and therapeutic targets from pathology specimens.

Gastric cancer is the fourth most common malignancy in the world, and mortality due to gastric cancer is second only to that from lung cancer. 'Transcriptome dissection' is a detailed analysis of the entire expressed transcripts from a cancer, for the purpose of understanding the precise molecular mechanism of pathogenesis. Serial analysis of gene expression (SAGE) is a suitable technique for performing transcriptome dissection. Gastric cancers of different stages and histology were analyzed on SAGE, and one of the largest gastric cancer SAGE libraries in the world was created (GEO accession number GSE 545). Through SAGE, many candidate genes have been identified as potential diagnostic and therapeutic targets for the treatment of gastric cancer. Regenerating islet-derived family, member 4 (Reg IV) participated in 5-fluorouracil (5-FU) resistance and peritoneal metastasis, and its expression was associated with an intestinal phenotype of gastric cancer and with endocrine differentiation. GW112 expression correlated with advanced tumor stage. Measurement of Reg IV and GW112 levels in sera indicated a sensitivity of 57% for detection of cancer. SPC18 participated in tumor growth and invasion through transforming tumor growth factor-alpha upregulation. Palate, lung, and nasal epithelium carcinoma-associated protein (PLUNC) was a useful marker for gastric hepatoid adenocarcinoma. Expression of SOX9, HOXA10, CDH17, and loss of claudin-18 expression were associated with an intestinal phenotype of gastric cancer. Information obtained from transcriptome dissection greatly contributes to diagnosis and treatment of gastric cancer.