To identify the genes involved in esophageal carcinogenesis, we compared gene expression profiles in esophageal squamous cell carcinoma (ESCC) and matched normal esophageal epithelial tissues. Differential display analysis revealed significant changes in the expression of 26 genes; 21 genes were upregulated and 5 genes were downregulated. The differentially expressed genes included those associated with cellular metabolism, cell structure, transcription, proliferation, apoptosis, signal transduction, complement pathway, and cell-cell adhesion. The differential expression of these genes was confirmed by reverse Northern blot analysis. Reverse transcription PCR analysis of ESCC and matched normal esophageal tissues provided the first evidence that melanoma metastasis clone D (MEMD), a gene similar to oncostatin M receptor beta, and KIAA0471 gene products are upregulated in ESCCs. Intriguingly, KIAA0471, a novel gene product, is upregulated in esophageal tumors showing nodal invasion. Identification of these differentially expressed genes in esophageal tumors adds to the repertoire of genes associated with esophageal carcinogenesis and they may thus serve as potential novel molecular targets for diagnosis and therapy. Further characterization of known and unknown differentially expressed cDNAs identified in this study may provide significant clues for understanding the molecular mechanisms underlying esophageal tumorigenesis. (C) 2003 Elsevier Science (USA). All rights reserved.