APC hypermethylation for early diagnosis of colorectal cancer: a meta-analysis and literature review

Oncotarget. 2017 Jul 11;8(28):46468-46479. doi: 10.18632/oncotarget.17576.

Abstract

Adenomatous polyposis coli (APC) promoter hypermethylation has been frequently observed in colorectal cancer (CRC). The association between APC promoter methylation and clinicopathological significance in CRC is under investigation. We performed a meta-analysis to quantitatively evaluate the significance of APC methylation in CRC. The study included a total of 24 articles and 2025 CRC patients. The frequency of APC promoter hypermethylation was significantly higher in colorectal adenoma than in normal colorectal tissue, OR was 5.76, 95% CI, 2.45-13.56; p<0.0001, I2=0%. APC promoter more frequently hypermethylated in CRC stage I compared to normal colorectal tissue, OR was 13.42, 95% CI, 3.66-49.20; p<0.0001, I2=31%. The risk of incidence of CRC was significantly correlated to APC promoter hypermethylation, pooled OR was 9.80, 95%CI, 6.07-15.81; p<0.00001, I2=43%. APC methylation was not associated with grade, stage of CRC as well as tumor location, patients' gender, and smoking behavior. The results indicate that APC promoter hypermethylation is an early event in carcinogenesis of CRC, could be a valuable diagnostic marker for early-stage CRC. APC methylation is not significantly associated with overall survival in patients with CRC. APC is a potential drug target for development of personalized treatment.

Keywords: APC; adenoma; adenomatous polyposis coli; biomarker; methylation.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Adenomatous Polyposis Coli Protein / genetics*
  • Biomarkers, Tumor
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / genetics*
  • DNA Methylation*
  • Early Detection of Cancer
  • Epigenesis, Genetic
  • Female
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Neoplasm Grading
  • Neoplasm Staging
  • Odds Ratio
  • Promoter Regions, Genetic
  • Publication Bias
  • Sex Factors

Substances

  • Adenomatous Polyposis Coli Protein
  • Biomarkers, Tumor