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

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.

SUBMITTER: Liang TJ

PROVIDER: S-EPMC5542282 | biostudies-other | 2017 Jul

REPOSITORIES: biostudies-other

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Project description:BACKGROUND:The RUNX family, which is composed of RUNX1, RUNX2, and RUNX3, is a sequence-specific transcription factor family and is closely involved in a variety of cellular processes including development, differentiation, participation in the regulation of p53-dependent DNA damage response and/or tumorigenesis. Emerging evidence indicates that RUNX3 is a candidate tumor suppressor in several types of human tumors including colorectal cancer (CRC). However, the correlation of RUNX3 inactivation with CRC remains unclear. In the study reported here, we conducted a systematic review and meta-analysis to quantitatively evaluate the effects of RUNX3 hypermethylation/expression on the incidence of CRC. METHODS:A detailed search of the literature was made using Medline(®) and Web of Science for related research publications written in English. The methodological quality of the studies was also evaluated. The data were extracted and assessed by two reviewers independently. Analyses of the pooled data were performed. Odds ratios (ORs) and hazard ratios were calculated and summarized, respectively. RESULTS:A final analysis of 1,427 CRC patients from eleven eligible studies was performed. We observed that RUNX3 hypermethylation was significantly higher in CRC than in normal colorectal mucosa. The pooled OR from six studies comprising 289 CRC and 188 normal colorectal mucosa was OR =0.07 (confidence interval [CI] =0.03-0.18, P<0.00001). Aberrant RUNX3 hypermethylation/expression was significantly higher in advanced CRC than in early staged CRC (OR =0.54, CI =0.41-0.71, P<0.0001). Aberrant RUNX3 hypermethylation/expression was also significantly higher in microsatellite instability (MSI)-positive CRC than in MSI-negative CRC (OR =0.44, CI =0.3-0.66, P<0.0001). In addition, CRC patients with RUNX3 hypermethylation or lacking RUNX3 protein expression had a lower survival rate than those without RUNX3 hypermethylation or those who did not express RUNX3 protein. CONCLUSION:The results of this meta-analysis suggest that RUNX3 hypermethylation is associated with an increased risk of CRC, increased risk of progression of CRC, and a poorer CRC survival rate. RUNX3 hypermethylation, which induces the inactivation of RUNX3 gene, plays an important role in colorectal carcinogenesis, high levels of MSI, as well as CRC progression and development.

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

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