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To further investigate the molecular mechanism of esophageal carcinogenesis, screen out and validate the genes expressed differently in esophageal cancer. mRNA differential display (DD-PCR) was employed to search differently expressed fragments, some of which were cloned and sequenced. By homology analysis in GenBank, corresponding homologous genes of those fragments were found. The corresponding genes of those differently expressed fragments were validated by Real-time quantitative PCR. By DD-PCR, one EST was identified to be Homo sapiens signal transducer and activator of transcription 2 (stat2) gene. The mRNA analysis result by real-time quantitative PCR showed that the expression level of stat2 gene in esophageal cancer (n=16, p<0.05), gastric cancer (n=12, p<0.05) and lung cancer tissues (n=16, p<0.05) were significantly higher than that in normal tissues. The ORF of stat2 gene was 2556 base pair long and encodes 852 amino acids. The molecular weight was about 97.9 KD. The over-expression of stat2 gene in esophageal cancer, gastric cancer and lung cancer may indicate an important role in these carcinogenesis.