Novel SFRP2 DNA Methylation Profile Following Neoadjuvant Therapy in Colorectal Cancer Patients with Different Grades of BMI

Abstract

The relationship between body weight and different cancers is now well-recognized and among such cancers, colorectal cancer (CRC) is reported most frequently. Our group recently published findings, through an epigenome-wide association study, suggesting that body mass index (BMI) could act as a relevant risk factor in the CRC. In addition, aberrant SFRP2 methylation is one of the major mechanisms for Wnt signaling activation in CRC. Conversely, neoadjuvant chemo-radiotherapy appears to alter the rectal cancer epigenome. This study was aimed to evaluate the effect of obesity, measured by BMI, on the methylation of SFRP2 in tumor samples of patients with CRC. Non-treated CRC patients and CRC patients treated with pre-operative neoadjuvant therapy from 2011 to 2013 were included and classified by BMI < 25.0 kg/m2 and BMI > 25.0 kg/m2. SFRP2 DNA methylation in tumor samples was measured by pyrosequencing. Our findings suggest a possible interaction between SFRP2 methylation levels and BMI in CRC tumor samples. The correlation of SFRP2 hypomethylation with an elevated BMI was stronger within the non-treated CRC patient group than within the treated CRC patient group. We have successfully demonstrated that the beneficial association of tumor SFRP2 hypomethylation is dependent on patient BMI in non-treated CRC, suggesting a possible tumor suppressor role for SFRP2 in overweight and obese patients. Additional studies of clinical pathologies would be necessary to strengthen these preliminary results