Investigation of GHSR and GHRL Methylation in Colorectal Cancer

Abstract

Aim: To investigate GHSR and GHRL methylation in 73 pairs of colorectal cancer (CRC) tissues and healthy adjacent mucosa. Methods: Methylation was assessed with methylation-sensitive high-resolution melting. Results:GHSR was significantly hypermethylated in CRC tissues than in healthy mucosa (p < 1 × 10^-5), but no significant changes of GHRL methylation were observed. GHSR hypermethylation was already detectable at the adenoma stage and maintained in later stages independently of age, gender, anatomical location, histological grading, MLH1 deficiency, as well as of major polymorphisms in folate-pathway genes, yielding an area under the curve of 0.824 for discriminating cancers from respective non-neoplastic mucosa specimens. Conclusion:GHSR hypermethylation occurs early in CRC, but is not paralleled by significant changes of GHRL methylation.

Keywords::

• colorectal cancer
• DNA methylation
• epigenetics
• folate polymorphisms
• GHRL
• GHSR

Financial & competing interests disclosure

This work was supported by researcher’s intramural funds (ATENEO Funds, University of Pisa). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by researcher’s intramural funds (ATENEO Funds, University of Pisa). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.