MiRNA-181d Expression Correlates in Tumor versus Plasma of Glioblastoma Patients—the Base of a Preoperative Stratification Tool for Local Carmustine Wafer Use

WORLD NEUROSURGERY(2022)

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摘要
OBJECTIVE: Patients with a low micro-RNA-181d (miRNA-181d) level in glioblastoma tissue benefit most of carmustine wafer use. The study compares preoperative miRNA-181d plasma and tumor expression. This may form the base to decide, from a preoperative blood test, if carmustine wafer implantation is recommendable. METHODS: A total of 60 patients suffering from glioblastoma treated between 2018 and 2020 were enrolled prospectively. Preoperatively, blood was drawn and the plasma was isolated. Tumor specimens were collected. Blood samples from 30 healthy individuals served as a reference. MiRNA-181d expression in plasma and tumor were acquired as fold change, using quantitative reverse transcription-polymerase chain reaction. Results were correlated with relevant demographic, clinical, and histopathologic aspects of the cohort. Further factors like tumor volume as well as blood panel results were considered. The Cancer Genome Atlas analysis was performed to investigate specific miRNA-181d-protein interactions to elude how miRNA-181 impact therapy response to carmustine. RESULTS: Patients with glioblastoma showed a significant overexpression of miRNA-181d compared with healthy individuals (P=0.029). There was a significant correlation between miRNA-181d expression in tumor tissue and plasma (P = 0.001, R = 0.51). The sensitivity of low miRNA-181d expression in plasma predicting low miRNA-181d tumor expression was 76.6%. Tumor volume, preoperative medication, and items of blood panel analysis did not influence the prognostic value of plasma miRNA-181d expression. The Cancer Genome Atlas analysis revealed 8 potential protein targets to be regulated by miRNA-181d. CONCLUSION: miRNA-181d seems to be a potential molecular marker that can reliably be detected in blood samples of patients with glioblastoma. It should therefore prospectively be evaluated as a potential preoperative prognostic marker regarding carmustine wafer implantation.
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关键词
Carmustine, Glioblastoma, Liquid biopsy, micro-RNA, miRNA-181d
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