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ObjectiveTo discover and identify differentially expressed genes associated with colorectal adenoma formation and the role of RegⅣ in colorectal adenoma differentiation.MethodsA subtracted cDNA library was constructed with cDNAs that were isolated from either the normal mucosa or adenoma tissue of a single patient. Suppressive subtractive hybridization (SSH) combined with virtual north blotting was used to characterize differentially expressed genes and contigs were assembled by electronic cloning (in silico cloning) with the EST database. Semi-quantitative RT-PCR was performed in 9 colorectal adenomas.ResultsThe amino acid sequence was determined with open reading frame (ORF) prediction software and was found to be 100% homologous to the protein product of RegⅣ (a novel gene isolated from a large inflammatory bowel disease library). RegⅣ was found to be highly expressed in all of the adenoma samples (9/9) compared with the normal mucosa samples, while 5/6 cases showed RegⅣ to be more strongly expressed in adenocarcinoma.Conclusion RegⅣ may play an important role in the initiation of colorectal adenoma differentiation, and its detection may be useful in the early diagnosis of colorectal adenoma formation.