title: Clinicopathological significance and potential drug target of O6-methylguanine-DNA methyltransferase in colorectal cancer: a meta-analysis.
abstract: Emerging evidence indicates that O(6)-methylguanine-DNA methyltransferase (MGMT) is a candidate for tumor suppression in several types of human tumors including colorectal cancer (CRC). However, the correlation between MGMT hypermethylation and clinicopathological characteristics of CRC remains unclear. In this study, we conducted a systematic review and meta-analysis to quantitatively evaluate the effects of MGMT hypermethylation on the incidence of CRC and clinicopathological characteristics. A comprehensive literature search was done from Web of Science, the Cochrane Library Database, PubMed, EMBASE, CINAHL, and the Chinese Biomedical Database for related research publications written in English and Chinese. Methodological quality of the studies was also evaluated. Analyses of pooled data were performed with Review Manager 5.2. Odds ratio (OR) and hazard ratio (HR) were calculated and summarized, respectively. Final analysis from 28 eligible studies was performed. MGMT hypermethylation is found to be significantly higher in CRC than in normal colorectal mucosa, the pooled OR from 13 studies including 1085 CRC and 899 normal colorectal mucosa, OR = 6.04, 95 % confidence interval (CI) = 4.69-7.77, p < 0.00001. MGMT hypermethylation is also significantly higher in colorectal adenoma than in normal colorectal mucosa, but it is significantly less compared to that in CRC patients. Interestingly, MGMT hypermethylation is correlated with sex status and is significantly higher in female than in male. MGMT hypermethylation is also associated with high levels of microsatellite instability (MSI). The pooled HR for overall survival (OS) shows that MGMT hypermethylation is not associated with worse survival in CRC patients. The results of this meta-analysis suggest that MGMT hypermethylation is associated with an increased risk and high levels of MSI and may play an important role in CRC initiation. However, MGMT hypermethylation may play an important role in the early stage of CRC progression and development, as well as having limited value in prediction of prognosis in CRC patients. We also discussed that MGMT may serve as a potential drug target of CRC.
authors.affiliation: Department of Coloproctology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People's Republic of China.
authors.forename: Chen-Guo
authors.initials: CG
authors.lastname: Zheng
authors.forename: Chun
authors.initials: C
authors.lastname: Jin
authors.forename: Le-Chi
authors.initials: LC
authors.lastname: Ye
authors.forename: Nian-Zhao
authors.initials: NZ
authors.lastname: Chen
authors.forename: Zong-Jing
authors.initials: ZJ
authors.lastname: Chen
mesh_terms: D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D009154:Mutation; D009367:Neoplasm Staging; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis; D011401:Promoter Regions, Genetic
chemical_list: D006147:Guanine; C008449:O-(6)-methylguanine; D019853:O(6)-Methylguanine-DNA Methyltransferase