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VALIDATION OF GHSR METHYLATION AS A BIOMARKER OF COLORECTAL CANCER
Fabio Coppedè^*, Andrea Stoccoro, Alessandro Lazzarotti, Maria Rosaria Ritacco, Roberto Spisni, Lucia Migliore
University of Pisa, Pisa, Italy
Hypermethylation of the growth hormone secretagouge receptor (GHSR) gene was recently proposed as a common epigenetic alteration of high diagnostic value in a broad spectrum of cancers, but only a single study addressed this issue in colorectal cancer (CRC) specimens. In order to validate GHSR hypermethylation as a CRC biomarker and to further address its correlation with CRC clinical features, we compared 73 DNA samples extracted from CRC tissues and 73 DNA samples obtained from the apparently healthy colonic mucosa of the same patients. Very interestingly we observed a statistically significant hypermethylation of GHSR in tumor tissues than in healthy mucosa (51.3% vs. 20.5%, P < 5 x 10^-7). No correlation was observed between GHSR hypermethylation in tumor DNA samples and tumor stage, size, location, or patient's age and gender, indicating that this is an early epigenetic event already observable at the adenoma stage. In the normal colonic mucosa tissue GHSR showed an average methylation of 20.5%, and we observed a significant correlation with increasing age (r = 0.34, P = 0.003). We are currently investigating the correlation between GHSR methylation and polymorphic variants of genes involved in DNA methylation reactions, including DNA methyltransferases and folate-related genes. Present results confirm GHSR methylation as a strong epigenetic biomarker of CRC.

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