Aberrant hypermethylation of OGDHL gene promoter in sporadic colorectal cancer

Curr Probl Cancer. 2020 Feb;44(1):100471. doi: 10.1016/j.currproblcancer.2019.03.001. Epub 2019 Mar 16.

Abstract

Background: Aberrant methylation patterns of certain genes including tumor suppressors, a major epigenetic event, contribute mainly to tumorigenesis. Promoter CpG island methylation in Oxoglutarate dehydrogenase like (OGDHL) gene has been reported to reduce gene expression and hence apoptosis induction. This gene has been shown to be involved in colorectal cancer progression. In the present study, we investigated methylation status of OGDHL gene promoter in patients with colorectal cancer and evaluated its potential as a diagnostic biomarker.

Methods and material: After collecting clinicopathologic data of patients, tumor and matched tumor free margin samples were obtained from 40 individuals; total genomic DNA was extracted and subjected to bisulfite modification. Methylation status of the gene promoter was studied using quantitative methylation-specific PCR method. Finally, its potential as a diagnostic biomarker was evaluated by receiver operating characteristic curve analysis.

Results: There was not any significant correlation for clinicopathologic features including tumor stage, grade, size, and location with methylation status of OGDHL promoter. However, a significant high methylation level was observed in tumoral tissues compared with nontumoral marginal samples (P < 0.0001). Moreover, receiver operating characteristic curve analysis revealed 97.5% sensitivity and 95%, specificity for OGDHL promoter methylation in a cut off of 27.37% methylation as a biomarker for colorectal cancer.

Conclusion: The promoter of OGDHL gene is hypermethylated in colorectal cancer and might be considered as a biomarker for its development.

Keywords: Colorectal cancer; Epigenetic; OGDHL; Oxoglutarate dehydrogenase like; methylation.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Carcinogenesis / genetics
  • Case-Control Studies
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / surgery
  • CpG Islands / genetics
  • DNA Methylation*
  • Epigenesis, Genetic
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Ketoglutarate Dehydrogenase Complex / genetics*
  • Male
  • Middle Aged
  • Promoter Regions, Genetic / genetics

Substances

  • Biomarkers, Tumor
  • Ketoglutarate Dehydrogenase Complex
  • OGDHL protein, human