The Association Between <i>MGMT</i> Promoter Methylation and Patients with Gastric Cancer: A Meta-Analysis

Yuan, Xiaolong; Xu, Jifei; Fang, Weiyang; Zhao, Zhenfeng; Wang, Fan; Tong, Zhuting

doi:10.1089/gtmb.2016.0284

Cited by 5 publications

(3 citation statements)

References 22 publications

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“…On the correlation of methylation with overall survival, 3-OS and 5-OS were significantly lower in patients harbouring MGMT methylation compared to negative ones. Loss of MGMT expression has a significant impact on various types of cancers, mainly colorectal cancer [16,[24][25][26]. Hence, Ahmed et al noted that MGMT expression was significantly correlated with tumor stage and metastatic status [16].…”

Section: Discussionmentioning

confidence: 99%

ERCC1 and MGMT Methylation as a Predictive Marker of Relapse and FOLFOX Response in Colorectal Cancer Patients from South Tunisia

Jamai

Gargouri

Selmi

et al. 2023

Genes

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Genetic and epigenetic modifications present a major cause of relapse and treatment failure in colorectal cancer. This study aims to appreciate the prognostic and predictive value of ERRC1 and MGMT methylation. We also studied the prognostic impact of the ERCC1 rs11615 polymorphism as well as its expression. Methylation profiles of ERCC1 and MGMT were tested by methylation-specific PCR. A polymorphism of ERCC1 was studied using PCR-RFLP and its expression was examined by immunohistochemistry. ERCC1 was methylated in 44.6% of colorectal adenocarcinoma while MGMT was methylated in 69% of cases. MGMT methylation was strongly associated with lymph node metastasis, lymph invasion, venous invasion, perineural invasion, distant metastasis and relapse. Patients with methylation of both genes were more likely to have a poor prognosis and display chemoresistance. IHC analysis revealed that ERCC1 staining was noted in 52.8% of colorectal adenocarcinoma and inversely related to distant metastasis and cancer recurrence. Kaplan Meier analysis revealed that the worst overall survival was significantly associated with ERCC1 and MGMT methylation while decreased ERCC1 expression and T/T genotype exhibited the best overall survival. The methylation of MGMT, alone or combined with ERCC1, is predictive for poor prognosis, short overall survival and chemotherapy response in colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

ERCC1 and MGMT Methylation as a Predictive Marker of Relapse and FOLFOX Response in Colorectal Cancer Patients from South Tunisia

Jamai

Gargouri

Selmi

et al. 2023

Genes

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“…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].…”

Section: Discussionmentioning

confidence: 99%

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

Tan

2020

Bioscience Reports

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Background: O6-methylguanine-DNA methyltransferase (MGMT) is a specific DNA damage reversal repair protein. The influence of MGMT status on alkylating agent sensitivity in patients with neuroendocrine neoplasms (NENs) is controversial. We conducted a meta-analysis to assess the influence of MGMT status on the therapeutic sensitivity of alkylating agents in patients with NENs. Methods: We searched PubMed, EmBase, and Cochrane library public databases through 3 July 2019. The objective response rate (ORR) was the outcome data of interest. Subgroup analysis was performed according based on MGMT methylation and expression of MGMT protein. Results: Eleven studies were included in the meta-analysis. The proportion of patients with NENs that achieved an ORR after alkylating agent treatment was higher in the MGMT-deficient group than the non-deficient group (OR: 5.00; 95% CI: 3.04–8.22; P < 0.001; I2: 3%). Similar results were noted in the MGMT methylation and MGMT protein expression subgroups. Conclusion: Patients with NENs and MGMT methylation or low protein expression had a higher ORR proportion than patients without MGMT methylation or high protein expression. The MGMT status can be used as a biological indicator of the response to alkylating agent treatment in patients with NENs.

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“…So far, several methylation biomarkers have been reported in GC. For example, a meta‐analysis of 14 studies showed that MGMT promoter methylation could play an important role in gastric carcinogenesis (Yuan et al, ). Furthermore, DNA hypermethylation of several tumor‐suppressor genes such as CDH1 , CDKN2A , MLH1 , RUNX3 , and EIF4E was associated with gastric carcinogenesis (Ge et al, ; Hu, Qin, Zhang, Ye, & Huang, ).…”

Section: Introductionmentioning

confidence: 99%

GHSR DNA hypermethylation is a new epigenetic biomarker for gastric adenocarcinoma and beyond

Foroughi

Talebi

Haji

et al. 2019

Journal Cellular Physiology

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Aberrations of DNA methylation are early events in the development of tumors. In this study, we investigated the DNA methylation status of growth hormone secretagogue receptor (GHSR), a promising pan‐cancer biomarker, in gastric cancer (GC). Initially, data sets from DNA methylation and gene expression studies available at Gene Expression Omnibus (GEO) were analyzed. Confirmation was done on primary tumor specimens and adjacent normal stomach tissue samples. Both analyses showed significant hypermethylation of GHSR. For further validation, The Cancer Genome Atlas data on stomach cancer was used. A receiver operating characteristic curve analysis yielded an area under the curve value of 0.85, corroborating its usefulness as a diagnostic marker. A genome‐wide comethylation analysis revealed several correlated genes. CREB1 was found to act as an upstream regulator of this gene network. Furthermore, GHSR methylation was found to be a biomarker in several other tumor entities, namely cancers of the bladder, endometrium, esophagus, head and neck, liver, thyroid, kidney, and ovary. Our findings along with previous reports on other types of cancer suggest a high potential of GHSR gene methylation as a pan‐cancer biomarker, which could be considered for liquid biopsy applications.

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The Association Between MGMT Promoter Methylation and Patients with Gastric Cancer: A Meta-Analysis

Abstract: Our findings provide evidence that MGMT promoter methylation could play an important role in gastric carcinogenesis and may serve as an important biomarker for gastric cancer progression.

Cited by 5 publications

References 22 publications

ERCC1 and MGMT Methylation as a Predictive Marker of Relapse and FOLFOX Response in Colorectal Cancer Patients from South Tunisia

ERCC1 and MGMT Methylation as a Predictive Marker of Relapse and FOLFOX Response in Colorectal Cancer Patients from South Tunisia

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

GHSR DNA hypermethylation is a new epigenetic biomarker for gastric adenocarcinoma and beyond

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