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.
Highlights
Considering the correlation between the secreted frizzled-related protein type 2 (SFRP2) methylation status and body mass index (BMI) in CRC patients [14], together with the potential effect of neoadjuvant treatment on DNA methylation pattern; we propose that SFRP2 methylation could be associated with specific clinical outcome of CRC patients and this relationship could be affected by BMI or treatment
We initiated our analysis based on previous data of the SFRP2 promoter performed and published by our group and obtained from the Infinium Human Methylation 450 BeadChip array [14].The study sequence of the SFRP2 promoter used in our analysis showed seven CpG sites in the position −1500, relative to the expected transcription start site (+1),which was utilized to determine the methylation status of the SFRP2 promoter (Figure 1a)
The results of our study demonstrated that decreased SFRP2 methylation in CRC was associated with an increased BMI
Summary
We aimed to evaluate the SFRP2 methylation status in both CRC tissue and adjacent tumor-free tissue from 75 CRC patients, by pyrosequencing after bisulfite treatment. FHRoPw2 estvaetru,sinactchoisrdcilnagsstiofictahteiotunm, moroslot cpaattiioenn.t Ftiursmt oorfsaalml, pwleesowbesreervdeedrivtheadt fSroFmRPt2hemretchtuymlat.ion was significantly higher on the right-sided CRC (57.33P%r)im, aasrycormecptaalrecadntcoerthreqlueifrte-ssidspedecCifiRcCsu(r3g6i.c6a0l%tr)e.aHtmowenetv(etro,tainl mtheisocrleacstsailfiecxactisoino,nm, porsetcepdaetidenbty tnuemooardsjuavmapnltersawdieortehedrearpivyeodrfcrhoemmtohreardeicottuhmer.apy); so we aimed to evaluate whether the neoadjuvant therapy could be affecting the methylation levels. Within the by neoadjuvant radiotherapy or chemoradiotherapy); so we aimed to evaluate whether the neoadjuvant therapy could be affecting the methylation levels
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