Association of MGMT promoter methylation with tumorigenesis features in patients with ovarian cancer: A systematic meta‐analysis

Abstract

BackgroundThe MGMT is a key tumor suppressor gene and aberrant promoter methylation has been reported in many cancers. However, the relationship between MGMT promoter methylation and ovarian cancer remains controversial. This meta‐analysis was first conducted to estimate the clinical significance of MGMT promoter methylation in ovarian carcinoma.MethodsLiterature search was performed in the PubMed, Embase, EBSCO and Cochrane Library databases. The pooled odds ratio (OR) and their corresponding 95% confidence interval (95% CI) were summarized.ResultsFinal 10 studies with 910 ovarian tissue samples were included in this meta‐analysis. MGMT promoter methylation was significantly higher in ovarian cancer than in normal ovarian tissues (OR = 4.13, 95% CI = 2.32–7.33, p < .001). The MGMT had a similar methylation status in cancer versus benign lesions and low malignant potential (LMP) samples (OR = 2.01, 95% CI = 0.67–6.04, p = .212; OR = 1.42, 95% CI = 0.46–4.40, p = .543; respectively). MGMT promoter methylation was correlated with pathological types in which it was significantly lower in serous cancer than in nonserous cancer (OR = 0.29, 95% CI = 0.14–0.59, p = .001). The methylation of the MGMT promoter was not associated with clinical stage and tumor grade (OR = 1.46, 95% CI = 0.71–3.02, p = .301; OR = 1.13, 95% CI = 0.51–2.46, p = .767; respectively).Conclusions MGMT promoter methylation may be correlated with the tumorigenesis of ovarian cancer. It was associated with tumor histotypes, but not correlated with clinical stage and tumor grade. More prospective studies with lager sample sizes are necessary in the future.

Distinct DNA Methylation Profiles in Ovarian Tumors: Opportunities for Novel Biomarkers

“…The most interesting point is that these groups reclassified by clustering are very close to the histological classifications. This observation has been reported in previous studies [ 13 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ] in which a small number of cases or a small number of genes have been considered. Our work highlights and confirms the link between methylation and histotypes due to relatively high number of cases analyzed (95 ovarian carcinomas and 7 germ cell tumors) and to the selection of several genes involved in the carcinogenesis and ovarian development.…”

“…Aberrant hypermethylation of MGMT ( O -6-Methylguanine-DNA Methyl Transferase) is particularly interesting. This gene is involved in the repair of DNA damages and hypermethylation is observed in several neoplastic and preneoplastic conditions [ 35 , 42 ] Recently, a meta-analysis that evaluated the samples of 10 ovarian cancer studies showed the importance of MGMT methylation in ovarian cancers [ 26 ]. Our study confirms the high occurrence of MGMT methylation in ovarian cancers.…”

DNA Repair and Ovarian Carcinogenesis: Impact on Risk, Prognosis and Therapy Outcome

“…In general, defective homologous recombination repair (HR), non-homologous end-joining (NHEJ), mismatch repair (MMR), base excision repair (BER), and disorders in nucleotide excision repair (NER) are typically reflected in OvC origin, pathogenesis and response to chemotherapy [20,24], whereas direct reversal of lesions is in connection with OvC addressed scarcely. Interestingly, there is sufficient evidence on the participation of all DNA repair pathways in ovarian tumorigenesis due to complex exposures from environment [25,26]. Main DNA repair pathways relevant in ovarian carcinogenesis and their role in cellular biology are illustrated in Figure 1.…”

Genome‐wide DNA methylome analysis reveals methylation subtypes with different clinical outcomes for acute myeloid leukemia patients

“…To investigate the role of methylation in cancers, most studies focused on the single genome context, such as CGI, while neglected CpG sites in other regions. [23][24][25] In the present study, we integrated the genome-wide CpG methylation profiles and identified the methylation subtypes for AML samples using COCA method. Analyzing the clinical outcomes for samples of the three subtypes, we found that subtype 1 showed significantly better prognosis and subtypes 2 and 3 have worse prognosis.…”

“…For the analysis of methylation profiles, most studies focused on the CGIs while ignored the methylation pattern on other genome regions. [23][24][25] In this study, we used the COCA method to identify the AML subtypes based on the methylation profiles at different genomic contexts, including CGI, CGI shore, CGI shelf, and opensea. As described above, there was significant different survival rate between the three subtypes.…”