MicroRNA-181 family predicts response to concomitant chemoradiotherapy with temozolomide in glioblastoma patients.
MicroRNAs are endogenously expressed regulatory noncoding RNAs. Previous studies showed altered expression levels of several microRNAs in glioblastomas. In this study, we examined the expression levels of selected microRNAs in 22 primary glioblastomas and six specimens of adult brain tissue by real-time PCR method. In addition, we examined methylation status of MGMT promoter by methylation-specific real-time PCR, as this has been shown to be a predictive marker in glioblastomas. MGMT methylation status was not correlated with response to concomitant chemoradiotherapy with temozolomide (RT/TMZ). MiR-221 (p=0.016), miR-222 (p=0.038), miR-181b (p=0.036), miR-181c (p=0.043) and miR-128a (p=0.001) were significantly down-regulated in glioblastomas. The most significant change was observed for up-regulation in miR-21 expression in glioblastomas (p<0.001). MiR-181b and miR-181c were significantly down-regulated in patients who responded to RT/TMZ (p=0.016; p=0.047, respectively) in comparison to patients with progredient disease. Our data indicate for the first time that expression levels of miR-181b and miR-181c could serve as a predictive marker of response to RT/TMZ therapy in glioblastoma patients.
Slaby
O
O
Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic. slaby@mou.cz
Lakomy
R
R
Fadrus
P
P
Hrstka
R
R
Kren
L
L
Lzicarova
E
E
Smrcka
M
M
Svoboda
M
M
Dolezalova
H
H
Novakova
J
J
Valik
D
D
Vyzula
R
R
Michalek
J
J
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000235:genetics* / Q000628:therapy; D003131:Combined Modality Therapy; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005909:Glioblastoma / Q000235:genetics* / Q000628:therapy; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000032:analysis*; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000235:genetics
D014408:Biomarkers, Tumor; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide