Ann Dermatol.  2018 Apr;30(2):129-135. 10.5021/ad.2018.30.2.129.

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

• Qi F
• Yin Z
• Wang G
• Zeng S

• KMID: 2414672
• DOI: http://doi.org/10.5021/ad.2018.30.2.129

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.

Keyword

Blood; Melanoma; Methylation; MGMT; Prognosis; Therapeutics

MeSH Terms

Disease-Free Survival
Drug Therapy
Genes, Tumor Suppressor
Humans
Melanoma*
Methylation*
Multivariate Analysis
Odds Ratio
Prognosis

Figure

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  Fig. 1 Flow chart of a systematic literature search. MGMT: O6-methylguanine-DNA methyltransferase.

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  Fig. 2 Forest plot of the association between O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and melanoma. OR: odds ratio, CI: confidence interval.

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  Fig. 3 Subgroup analysis of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation by sample type in metastatic melanoma vs. normal controls. OR: odds ratio, CI: confidence interval.

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  Fig. 4 Subgroup analysis of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation by detection method in metastatic melanoma vs. normal controls. OR: odds ratio, CI: confidence interval, MSP: methylation specific polymerase chain reaction, QMSP: quantitative methylation-specific polymerase chain reaction.

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  Fig. 5 Forest plot of the association between O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and response to therapy in melanoma. OR: odds ratio, CI: confidence interval.

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