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

J 2011

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

LAKOMÝ, Radek, Jiří ŠÁNA, Simona HANKEOVÁ, Pavel FADRUS, Leoš KŘEN et. al.

Basic information

Original name

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

Authors

LAKOMÝ, Radek (203 Czech Republic, guarantor, belonging to the institution), Jiří ŠÁNA (203 Czech Republic, belonging to the institution), Simona HANKEOVÁ (203 Czech Republic, belonging to the institution), Pavel FADRUS (203 Czech Republic, belonging to the institution), Leoš KŘEN (203 Czech Republic, belonging to the institution), Eva LŽIČAŘOVÁ (203 Czech Republic, belonging to the institution), Marek SVOBODA (203 Czech Republic, belonging to the institution), Hana DOLEŽELOVÁ (203 Czech Republic, belonging to the institution), Martin SMRČKA (203 Czech Republic, belonging to the institution), Rostislav VYZULA (203 Czech Republic, belonging to the institution), Jaroslav MICHÁLEK (203 Czech Republic, belonging to the institution), Marian HAJDÚCH (203 Czech Republic) and Ondřej SLABÝ (203 Czech Republic, belonging to the institution)

Edition

Cancer Science, 2011, 1347-9032

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30200 3.2 Clinical medicine

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 3.325

RIV identification code

RIV/00216224:14110/11:00053884

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1111/j.1349-7006.2011.02092.x

UT WoS

000297202800010

Keywords in English

MGMT PROMOTER METHYLATION; SUPPRESSES TUMORIGENICITY; ANAPLASTIC ASTROCYTOMA; ADJUVANT TEMOZOLOMIDE; CELLS; CONCOMITANT; MICRORNA-21; PATHWAYS; SURVIVAL; RADIOTHERAPY

Abstract

V originále

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.

Citovat

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. 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.

@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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