MiR‐195, miR‐196b, miR‐181c, miR‐21 expression levels and O‐6‐methylguanine‐DNA methyltransferase methylation status are associated with clinical outcome in glioblastoma patients

• Published in: Cancer science 2011-12, Vol.102 (12), p.2186-2190
• Main Authors: Lakomy, Radek, Sana, Jiri, Hankeova, Simona, Fadrus, Pavel, Kren, Leos, Lzicarova, Eva, Svoboda, Marek, Dolezelova, Hana, Smrcka, Martin, Vyzula, Rostislav, Michalek, Jaroslav, Hajduch, Marian, Slaby, Ondrej
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological and medical sciences; biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Brain Neoplasms - diagnosis; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - mortality; Brain tumors; Cancer; Data processing; Disease-Free Survival; DNA Methylation; DNA Modification Methylases - genetics; DNA Modification Methylases - metabolism; DNA Repair Enzymes - genetics; DNA Repair Enzymes - metabolism; Female; Gene expression; Glioblastoma; Glioblastoma - diagnosis; Glioblastoma - genetics; Glioblastoma - metabolism; Glioblastoma - mortality; glioblastoma multiforme; Humans; Kaplan-Meier Estimate; Male; Medical sciences; Melting; Methylation; MicroRNAs - biosynthesis; Middle Aged; miRNA; Neurology; non-coding RNA; O6-methylguanine-DNA methyltransferase; Original; Post-transcription; Prognosis; Promoter Regions, Genetic; Promoters; Retrospective Studies; Risk factors; Surgery; Survival; Treatment Outcome; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Tumors; Tumors of the nervous system. Phacomatoses
• ISSN: 1347-9032; 1349-7006; 1349-7006
• DOI: 10.1111/j.1349-7006.2011.02092.x

Glioblastoma multiforme (GBM) is the most frequently occurring primary malignant brain tumor; patients with GBM often have a very poor prognosis and differing responses to treatment. Therefore, it is very important to find new biomarkers that can predict clinical outcomes and help in treatment decisions. MicroRNAs are small, non‐coding RNAs that function as post‐transcriptional regulators of gene expression and play a key role in the pathogenesis of GBM. In a group of 38 patients with primary GBM, we analyzed the expression of eight microRNAs (miR‐21, miR‐128a, miR‐181c, miR‐195, miR‐196a, miR‐196b, miR‐221, and miR‐222). In addition, we examined the methylation status of O‐6‐methylguanine‐DNA methyltransferase (MGMT) promoter by high‐resolution melting analysis, as this has been shown to be a predictive marker in GBM. MGMT methylation status correlated with progression‐free survival (P = 0.0201; log–rank test) as well as with overall survival (P = 0.0054; log–rank test). MiR‐195 (P = 0.0124; log–rank test) and miR‐196b (P = 0.0492; log–rank test) positively correlated with overall survival. Evaluation of miR‐181c in combination with miR‐21 predicted time to progression within 6 months of diagnosis with 92% sensitivity and 81% specificity (P