Prognostic value of MGMT methylation in colorectal cancer: a meta-analysis and literature review

Abstract

The development of colorectal cancer (CRC) spans about 5-10 years, making early detection and prevention beneficial to the survival of CRC patients. To address inconsistencies in evidence regarding O(6)-methylguanine-DNA-methyltransferase (MGMT) methylation as a potential prognostic factor in CRC, we conducted a meta-analysis to evaluate MGMT methylation in CRC patients. Fourteen studies were included in the meta-analysis after screening 120 articles. The following items were collected from each study: author, published year, country, patient gender, MGMT methylation status, and patients' disease progression. Pooled hazard ratios and odd ratios with 95% confidence intervals (CIs) were calculated using fixed or random effect models depending on the heterogeneity between studies. The overall survival of CRC patients was found not to be significantly associated with MGMT methylation. Further subgroup analysis showed that the frequency of MGMT methylation was significantly higher in CRC than in normal tissues (p < 0.00001). MGMT promoter in CRC patients was more frequently methylated than in adenoma patients. In addition, MGMT methylation was significantly increased in adenoma than in normal tissues (p < 0.0001). In conclusion, MGMT methylation is central to the development of cancer that involves a stepwise carcinogenesis of normal adenoma carcinoma cascade. However, MGMT methylation is not associated with the prognosis of CRC.

Base excision repair imbalance in colorectal cancer has prognostic value and modulates response to chemotherapy

“…Clinical trials for TMZ in CRC were designed to exploit the association between MGMT deficiency and increased sensitivity to temozolomide [ 41 , 42 ]. Indeed, MGMT promoter hypermethylation and low MGMT expression appear to be early events in CRC patients [ 43 ], consistently with our clinical results. In addition, concomitant downregulation of both MGMT and MPG correlate with an improved response to TMZ [ 44 ].…”

Different prognostic effect of CpG island methylation according to sex in colorectal cancer patients treated with adjuvant FOLFOX

“…We have recently reported that concurrent methylation in NEUROG1 and CDKN2A (p16) is associated with higher recurrence in colorectal cancer patients whereas CIMP classification based on the number of methylated markers was not [ 4 ]. Importance of individual gene methylation such as CHFR , MGMT , and SHISA3 has also been shown in other studies [ 6 , 10 , 11 ].…”

A novel DNA methylation panel accurately detects colorectal cancer independently of molecular pathway

“…Remarkably, higher SEPT9 promoter methylation was independently associated with increased DSS in CRC, whereas no prognostic value was depicted for the remainder gene promoters. A meta-analysis that included 14 studies showed that MGMT methylation status was not associated with CRC prognosis [47], whereas RASSF1A promoter methylation has been associated with poor prognosis, although when assessed in plasma samples [30]. Furthermore, CIMP status also did not disclose prognostic value in our study, which is in accordance with a recent metaanalysis that found no significant effect of CIMP status in DFS or OS in 8 out of 11 and in 13 out of 19 studies previously published, respectively [48].…”