Investigation of GHSR and GHRL methylation in colorectal cancer

Epigenomics. 2018 Dec;10(12):1525-1539. doi: 10.2217/epi-2018-0030. Epub 2018 Jul 2.

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: DNA methylation; GHRL; GHSR; colorectal cancer; epigenetics; folate polymorphisms.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / genetics*
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Colorectal Neoplasms / genetics*
  • DNA Methylation*
  • Epigenomics
  • Female
  • Folic Acid / metabolism
  • Ghrelin / genetics*
  • Humans
  • Male
  • Middle Aged
  • MutL Protein Homolog 1 / genetics
  • Neoplasm Staging
  • Polymorphism, Genetic / genetics*
  • ROC Curve
  • Receptors, Ghrelin / genetics*

Substances

  • Biomarkers, Tumor
  • GHRL protein, human
  • Ghrelin
  • MLH1 protein, human
  • Receptors, Ghrelin
  • Folic Acid
  • MutL Protein Homolog 1