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Association between MGMT status and response to alkylating agents in patients with neuroendocrine neoplasms: a
1Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing 100029, People's Republic of China.
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.
Insights
O6-methylguanine-DNA methyltransferase (MGMT) deficiency predicts better response to alkylating agents in neuroendocrine neoplasms (NENs). MGMT status serves as a key biomarker for predicting therapeutic sensitivity in NEN patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein.
- MGMT status's role in alkylating agent sensitivity for neuroendocrine neoplasms (NENs) remains debated.
- This meta-analysis investigates MGMT's influence on NEN treatment response.
Purpose of the Study:
- To evaluate the impact of MGMT status on the efficacy of alkylating agents in NEN patients.
- To determine if MGMT methylation or protein expression levels correlate with treatment outcomes.
- To establish MGMT as a potential predictive biomarker for NEN therapy.
Main Methods:
- A meta-analysis was conducted using data from PubMed, EmBase, and Cochrane Library.
- Searches were performed up to July 3, 2019.
- Objective response rate (ORR) was the primary outcome, with subgroup analyses for MGMT methylation and protein expression.
Main Results:
- Eleven studies were included, comprising patients with NENs treated with alkylating agents.
- Patients with MGMT deficiency showed a significantly higher ORR compared to those with MGMT sufficiency (OR: 5.00; 95% CI: 3.04-8.22; P < 0.001).
- Consistent findings were observed across subgroups analyzing MGMT methylation and protein expression.
Conclusions:
- MGMT methylation or low protein expression in NENs is associated with improved ORR to alkylating agents.
- MGMT status is a valuable biological indicator for predicting treatment response in NEN patients.
- These findings support the use of MGMT status in guiding NEN therapeutic strategies.
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