Prognostic value of TP53 expression and MGMT methylation in glioblastoma patients treated with temozolomide combined with other chemotherapies

Abstract

Objective To assess the recurrence interval and predictive significance of TP53 expression and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastomas treated with radiotherapy and combined chemotherapies, including temozolomide, lomustine, procarbazine and bevacizumab. Method We reviewed the clinical outcomes of 52 totally resected glioblastoma patients, who received conventional radiotherapy and temozolomide with other chemotherapeutic agents. Correlation of TP53 expression and MGMT promotor methylation with recurrence interval was analyzed using Kaplan Meier estimates. Results No significant association was found between MGMT promotor methylation and TP53 expression in glioblastomas (P-value = 0.158). Patients with non-methylated MGMT who received temozolomide chemotherapy with other chemotherapeutic agents showed significantly later recurrence (P-value = 0.007) compared with patients with non-methylated MGMT who received temozolomide alone. No significant difference was found in recurrence interval among glioblastoma patients with methylated MGMT who received temozolomide alone or with other chemotherapies (P-value = 0.667). Moreover, patients with non-TP53-expressing tumors who received temozolomide with other chemotherapies had significantly later recurrence (P-value = 0.04) compared with patients who received temozolomide alone. Conclusion Totally resected glioblastoma patients, with non-methylated MGMT or non-TP53-expressing tumors treated with radiotherapy and combined chemotherapies had a reduced chance of tumor recurrence and a more favorable outcome. Furthermore, both MGMT and TP53 are independent prognostic factors for glioblastoma.

Association Between CD204-Expressed Tumor-Associated Macrophages and MGMT-Promoter Methylation in the Microenvironment of Grade 4 Astrocytomas

“…MGMT is a DNA repair protein that reverses alkylation at the O 6 position of guanine, thereby neutralizing the cytotoxic effects of temozolomide (TMZ) alkylating agent. A lack of MGMT repair contributes to the progression of cancers through the accumulation of DNA mutations [ 19 , 20 ]. Because grade 4 astrocytomas started to develop resistant to TMZ treatment in MGMT -methylated tumors, the need to explore new therapeutic targets to increase sensitivity of tumor cells to TMZ becomes essential [ 21 ].…”