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

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.

Keywords: O6-methylguanine-DNA methyltransferase; alkylating agents; meta-analysis; neuroendocrine neoplasms.

Figure 1. PRISMA flow chart illustrating the selection of studies included in our analysis

Figure 2. Forest plot of ORR results comparing MGMT deficient and non-MGMT deficient patients with NENs after alkylating agent treatment

Figure 3. The funnel plot for assessing potential publication

Figure 4. Subgroup analysis of ORR results according to MGMT protein expression (subgroup 1) and detection of MGMT methylation (subgroup 2)