Profiling, comparison and validation of gene expression in gastric carcinoma and normal stomach

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Abstract
Gastric carcinoma is the fourth most common cause of cancer death worldwide but its molecular biology is poorly understood. We catalogued the genes expressed in two gastric adenocarcinomas and normal stomach, using serial analysis of gene expression (SAGE), and compared the profiles on-line with other glandular epithelia. Candidates were validated by Northern blotting and immunohistochemistry. A total of 29 480 transcripts, derived from 10 866 genes, were identified. In all, 1% of the genes were differentially expressed (fivefold difference plus P-value 0.01) between cancers and normal stomach. The most abundant transcripts included ribosomal and mitochondrial proteins, of which most were upregulated in the tumours, as were other widely expressed genes including transcription factors, signalling molecules (serine/threonine protein kinases), thymosin beta 10 and collagenase I. Transcripts abundant in normal stomach were functionally important, including gastrin, immunoglobulin alpha, lysozyme, MUC5, pS2 and pepsinogens, which were among 55 gastric-specific genes. Many transcripts were minimally characterized or new, some cancer-associated genes reflected their intestinal morphology, and some normal gastric genes had previously been considered as pancreatic carcinoma markers. The gastric carcinoma profiles resembled other tumours', supporting the existence of common cancer-associated targets. These data provide a catalogue from which to develop markers for better diagnosis and therapy of gastric carcinoma.