MiRNA-181d Expression Significantly Affects Treatment Responsesto Carmustine Wafer Implantation


BACKGROUND: Standard therapeutic protocols for glioblastoma, themost aggressive type of brain cancer, include surgery followed bychemoradiotherapy. Additionally, carmustine-eluting wafers can beimplanted locally into the resection cavity. OBJECTIVE: Toevaluate microRNA (miRNA)-181d as a prognostic marker ofresponses to carmustine wafer implantation. METHODS: A total of80 glioblastoma patients (40/group) were included in a matchedpair analysis. One group (carmustine wafer group) receivedconcomitant chemoradiotherapy with carmustine wafer implantation(Stupp protocol). The second group (control group) received onlyconcomitant chemoradiotherapy. All tumor specimens were subjectedto evaluations of miRNA-181d expression, results were correlatedwith further individual clinical data. The Cancer Genome Atlas(TCGA) dataset of 149 patients was used as an independent cohortto validate the results. RESULTS: Patients in the carmustinewafer group with low miRNA-181d expression had significantlylonger overall (hazard ratio [HR], 35.03, [95% confidenceinterval (CI): 3.50-350.23], P = .002) and progression-freesurvival (HR, 20.23, [95% CI: 2.19-186.86], P = .008) thanpatients of the same group with a high miRNA-181d expression.These correlations were not observed in the control group. Thenonsignificance in the control group was confirmed in theindependent TCGA dataset. The carmustine wafer group patientswith low miRNA-181d expression also had a significantly longerprogression-free (P = .049) and overall survival (OS) (P = .034),compared with control group patients. Gross total resectioncorrelated significantly with longer OS (P = .023). CONCLUSION:MiRNA-181d expression significantly affects treatment responsesto carmustine wafer implantation.