Clinical and Prognostic Significance of O⁶-Methylguanine-DNA Methyltransferase Promoter Methylation in Patients with Melanoma: A Systematic Meta-Analysis

Abstract

Tumor suppressor gene O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation has been reported in melanoma. However, the clinical and prognostic significance of MGMT promoter methylation in patients with melanoma remained to be determined. A systematic search was performed to identify eligible papers published. The overall odds ratios (ORs) or hazard ratios and their 95% confidence intervals were calculated. Final 12 eligible publications involving Caucasian population were performed in this study, including 1,071 metastatic melanoma patients, 154 primary melanoma patients, and 211 normal controls. MGMT promoter methylation was significantly higher in primary or metastatic melanoma than in normal controls (p<0.05). No difference of MGMT promoter methylation was found in primary and metastatic melanoma (p=0.432). When metastatic melanoma was compared to normal controls, subgroup analysis showed the correlation between MGMT promoter methylation and different sample materials (tissue: OR=7.01, p<0.001 and blood: OR=12.04, p=0.005). MGMT promoter methylation was not associated with response to drug therapy and the prognosis in overall survival and progression-free survival for multivariate analysis. Our results show that MGMT promoter methylation may be correlated with the increased risk of primary or metastatic melanoma. Based on blood samples, MGMT promoter methylation may become a noninvasive biomarker for the detection of metastatic melanoma. Further additional clinical studies are necessary.

Glioblastoma and malignant melanoma: Serendipitous or anticipated association?

“…A recent systemic meta‐analysis of 12 studies by Qi et al . noted that MGMT promoter methylation was higher in both primary MM and metastatic MM compared to normal controls 28 . Notably, they also found a higher incidence of MGMT promoter methylation in metastatic MM in blood samples compared to tissue samples, suggesting that MGMT promoter methylation could potentially be used as a biomarker for metastatic MM in blood samples 28 …”

Association between MGMT status and response to alkylating agents in patients with neuroendocrine neoplasms: a systematic review and meta-analysis

“…It has been shown that MGMT hypermethylation is associated with an increased risk of NSCLC [8]. MGMT promoter methylation is also associated with the occurrence and invasion of melanoma [9]. Furthermore, MGMT methylation can also be used as a biomarker to predict carcinogenesis in a variety of tumors [29][30][31][32].…”

“…O 6 -methylguanine-DNA methyltransferase (MGMT) is a widely studied specific DNA damage reversal repair protein that protects chromosomes from mutation, carcinogenesis, and cytotoxic effects of alkylating agents [7]. In previous studies, MGMT status was shown to be related to the occurrence and invasion of non-small cell lung cancer (NSCLC) [8], melanoma [9], malignant glioma [10], esophageal cancer [11], and prostate cancer [12]. MGMT also affected the chemotherapeutic effect of different tumor patients, but the results are controversial [8,9,13].…”

O6-Methylguanine-DNA Methyltransferase (MGMT): Challenges and New Opportunities in Glioma Chemotherapy

“…Because DNA methylation can inhibit transcription, methylation of MGMT promoter increases sensitivity to alkylating agents (27). Several studies have shown that methylation of MGMT promoter can predict whether alkylating agents can be of benefit in glioblastoma and low-grade gliomas (28)(29)(30)(31)(32)(33)(34)(35)(36)(37). Two other clinical trials have revealed that methylation status of MGMT promoter can predict the prognosis of glioma patients.…”