RESUMO
BACKGROUND: Although O(6)-methylguanine DNA methyltransferase (MGMT) promoter methylation status is an important marker for glioblastoma multiforme (GBM), there is considerable variability in the clinical outcome of patients with similar methylation profles. OBJECTIVE: We examined whether a MicroRNA (miRNA) signature can be identified for predicting clinical outcomes and helping in treatment decisions. METHODS: The differentially expressed miRNAs were evaluated in 6 pairs of short- (⩽ 450 days) and long-term survivors (> 450 days) by using microarray. Real time quantitative PCR (qRT-PCR) was applied to further verify screened miRNAs with a greater number of samples (n= 48). Meanwhile, functional interpretation of miRNA profile was carried out based on miRNA-target databases. In addition, MGMT promoter methylation status was tested by means of pyrosequencing (PSQ) testing. RESULTS: Six miRNAs were upregulated in the long-term survival group (fold change ⩾ 2.0, P< 0.05). The further verification by qRT-PCR indicated that the increase in let-7g-5p, miR-139-5p, miR-17-5p and miR-9-3p level in long-term survivors was statistically significant. Kaplan-Meier survival analysis showed that high expression of a prognostic 4-miRNA signature was significantly associated with good patient survival (p= 0.0012). The signature regulated signaling pathways including Calcium, MAPK, ErbB, mTOR and cell cycle involved in carcinogenesis from glial progenitor cell to primary GBM. CONCLUSIONS: The 4-miRNA signature was identified as an independent prognostic biomarker that identified patients who have a favorable outcome.
Assuntos
Biomarcadores Tumorais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Glioblastoma/genética , Glioblastoma/mortalidade , MicroRNAs/genética , Adulto , Idoso , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Metilação de DNA , Metilases de Modificação do DNA/genética , Feminino , Perfilação da Expressão Gênica , Glioblastoma/patologia , Glioblastoma/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Regiões Promotoras Genéticas , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
The vascular architecture of bone giant cell tumor was observed histologically with resin cast technique and scanning electron microscopy. Three types of capillaries were noted in the tumor tissue: extruding club-like capillary in the outer zone of the tumor; sinusoid capillary running disorderly in the intermediate zone; cecum capillary in the central zone. The pattern of vascular structure was believed to be correlated with tumor growth.