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Abstracto

O-6-Methylguanine-DNA Methyltransferase and Response to Alkylation Agents in Neuroendocrine Tumor: A Meta-Analysis

Heli Gao, Liang Liu, Zihao Qi, Huaxiang Xu, Wenquan Wang, Chuntao Wu, Shirong Zhang, Jinzhi Xu, Quanxing Ni, Xianjun Yu

Background The predictive significance of O-6-methylguanine-DNA methyltransferase promoter methylation for patients with neuroendocrine tumor and treated with alkylating agent chemotherapy remains controversial. This meta-analysis describes whether O-6- methylguanine-DNA methyltransferase expression and promoter methylation could help predict neuroendocrine tumor response to alkylating agent chemotherapy. Methods We conducted a systematic search in PubMed, EMBASE and the Cochrane library and identified articles describing a relationship between O-6-methylguanine-DNA methyltransferase status and patients with neuroendocrine tumor response to alkylating agent chemotherapy. Results Ten articles were included in our analysis. The O-6-methylguanine-DNA methyltransferase deficiency rate measured by immunohistochemistry was similar to the O-6-methylguanine-DNA methyltransferase promoter methylation rate measured by pyrosequencing. The O-6-methylguanine-DNA methyltransferase deficiency rate was higher in patients with pancreatic neuroendocrine tumor than in patients with gastrointestinal- neuroendocrine tumor (p<0.05). Neuroendocrine tumor with O-6-methylguanine-DNA methyltransferase deficiency/promoter methylation had a significantly longer progression-free survival when treated with alkylating agent chemotherapy, regardless of detection method: immunohistochemistry (hazard ratios 0.39, 95% confidence intervals 0.17–0.89) or pyrosequencing (hazard ratios 0.33, 95% confidence intervals 0.19–0.56). Also, neuroendocrine tumor with O-6-methylguanine-DNA methyltransferase deficiency had a better objective response rate to alkylating agent chemotherapy (by immunohistochemistry p=0.01, by pyrosequencing p=0.02). The subgroup analysis showed no significant association between O-6- methylguanine-DNA methyltransferase status and objective response rate in pancreatic neuroendocrine tumor patients. Conclusion O-6-methylguanine-DNA methyltransferase deficiency/promoter methylation predicts a favorable response to alkylating agents in neuroendocrine tumor patients, regardless of the O-6-methylguanine-DNA methyltransferase detection method. However, the predictive roles of O-6-methylguanine-DNA methyltransferase deficiency in pancreatic neuroendocrine tumor patients need further assessment.