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@article{957240, author = {Lakomý, Radek and Šána, Jiří and Hankeová, Simona and Fadrus, Pavel and Křen, Leoš and Lžičařová, Eva and Svoboda, Marek and Doleželová, Hana and Smrčka, Martin and Vyzula, Rostislav and Michálek, Jaroslav and Hajdúch, Marian and Slabý, Ondřej}, article_number = {12}, doi = {http://dx.doi.org/10.1111/j.1349-7006.2011.02092.x}, keywords = {MGMT PROMOTER METHYLATION; SUPPRESSES TUMORIGENICITY; ANAPLASTIC ASTROCYTOMA; ADJUVANT TEMOZOLOMIDE; CELLS; CONCOMITANT; MICRORNA-21; PATHWAYS; SURVIVAL; RADIOTHERAPY}, language = {eng}, issn = {1347-9032}, journal = {Cancer Science}, title = {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}, volume = {102}, year = {2011} }
TY - JOUR ID - 957240 AU - Lakomý, Radek - Šána, Jiří - Hankeová, Simona - Fadrus, Pavel - Křen, Leoš - Lžičařová, Eva - Svoboda, Marek - Doleželová, Hana - Smrčka, Martin - Vyzula, Rostislav - Michálek, Jaroslav - Hajdúch, Marian - Slabý, Ondřej PY - 2011 TI - 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 JF - Cancer Science VL - 102 IS - 12 SP - 2186-2190 EP - 2186-2190 SN - 13479032 KW - MGMT PROMOTER METHYLATION KW - SUPPRESSES TUMORIGENICITY KW - ANAPLASTIC ASTROCYTOMA KW - ADJUVANT TEMOZOLOMIDE KW - CELLS KW - CONCOMITANT KW - MICRORNA-21 KW - PATHWAYS KW - SURVIVAL KW - RADIOTHERAPY N2 - 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; logrank test) as well as with overall survival (P = 0.0054; logrank test). MiR-195 (P = 0.0124; logrank test) and miR-196b (P = 0.0492; logrank 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 < 0.0001). Our data confirmed that the methylation status of MGMT but also miR-21, miR-181c, miR-195, and miR-196b to be associated with survival of GBM patients. Above all, we suggest that the combination of miR-181c and miR-21 could be a very sensitive and specific test to identify patients at high risk of early progression after surgery. ER -
LAKOMÝ, Radek, Jiří ŠÁNA, Simona HANKEOVÁ, Pavel FADRUS, Leoš KŘEN, Eva LŽIČAŘOVÁ, Marek SVOBODA, Hana DOLEŽELOVÁ, Martin SMRČKA, Rostislav VYZULA, Jaroslav MICHÁLEK, Marian HAJDÚCH and Ondřej SLABÝ. 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. \textit{Cancer Science}. 2011, vol.~102, No~12, p.~2186-2190. ISSN~1347-9032. Available from: https://dx.doi.org/10.1111/j.1349-7006.2011.02092.x.
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