Abstract
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.
Highlights
Neuroendocrine neoplasms (NENs) are rarely tumors that originate from embryonic neuroendocrine cells that have neuroendocrine markers and can produce polypeptide hormones
There were similar results between the subgroups (Figure 4). This meta-analysis analyzed the relationship between methylguanine-DNA methyltransferase (MGMT) deficiency status and objective response rate (ORR) results in patients with neuroendocrine neoplasm (NEN) who received alkylating agent treatment
The results showed that the patients with NENs and MGMT methylation or low protein expression had a higher ORR than patients without MGMT methylation or high protein expression
Summary
Neuroendocrine neoplasms (NENs) are rarely tumors that originate from embryonic neuroendocrine cells that have neuroendocrine markers and can produce polypeptide hormones. The types of NENs are named based on site of origin and histology They frequently detected in the gastroenteropancreatic tract and bronchopulmonary tree, and typed as pancreatic, gastrointestinal and pulmonary NENs [1]. 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 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%).
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