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.
Highlights
Colorectal cancer (CRC) is one of the most common types of cancer worldwide and results from the accumulation of genetic and epigenetic alterations in colonic mucosa cells, which leads to colorectal adenoma, advanced to invasive and metastatic colorectal cancer (CRC)
Tumor suppressor genes associated with CRC include Adenomatous polyposis coli (APC), p53, BRAF and DCC [10, 15], and the loss of APC has been observed in approximately 70-80% of CRC [16,17,18,19], but the association between APC promoter methylation and clinicopathological significance in CRC is unclear
Our result indicated that the APC promoter is 5.76 times more frequently hypermethylated in adenoma www.impactjournals.com/oncotarget than in normal colorectal tissue
Summary
Colorectal cancer (CRC) is one of the most common types of cancer worldwide and results from the accumulation of genetic and epigenetic alterations in colonic mucosa cells, which leads to colorectal adenoma, advanced to invasive and metastatic CRC. Epigenetic alterations have been reported to play an important role in many cancers initiation, progression, and metastasis [1, 2]. DNA methylation within CpG island in promoter region of genes is associated with the loss of gene expression and is observed in many types of cancers including CRC. Loss of APC function leads to the destabilization and degradation of betacatenin, and the nuclear accumulation of beta-catenin results in the activation of T-cell factor/LEF target gene and initiates tumorgenesis [7, 8]. The present article aims to summarize the most recent findings concerning the use of epigenetic (mainly related to DNA methylation) biomarkers for CRC diagnosis, progression, and response to treatment
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