作者: Simon K. Hermansen , Mia D. Sørensen , Anker Hansen , Steen Knudsen , Alvaro G. Alvarado
DOI: 10.1371/JOURNAL.PONE.0188090
关键词:
摘要: Glioblastomas are among the most lethal cancers; however, recent advances in survival have increased need for better prognostic markers. microRNAs (miRNAs) hold great potential being deregulated glioblastomas and highly stable stored tissue specimens. Moreover, miRNAs control multiple genes representing an additional level of gene regulation possibly more prognostically powerful than a single gene. The aim study was to identify novel miRNA signature with ability separate patients into subgroups. Samples from 40 glioblastoma were included retrospectively; comparable on all clinical aspects except overall enabling be categorized as short-term or long-term survivors based median survival. A miRNome screening employed, profile developed using leave-one-out cross-validation. We found that expression patterns miRNAs; particularly four miRNAs: hsa-miR-107_st, hsa-miR-548x_st, hsa-miR-3125_st hsa-miR-331-3p_st could determine short- predicted accuracy 78%. Heatmap dendrograms dichotomized subgroups significant association univariate (HR 8.50; 95% CI 3.06–23.62; p<0.001) multivariate analysis 9.84; 2.93–33.06; p<0.001). Similar tendency seen Cancer Genome Atlas (TCGA) 2-miRNA miR-107 miR-331 (miR sum score), which only available TCGA. In TCGA, O6-methylguanine-DNA-methyltransferase (MGMT) unmethylated tumors low miR score had shortest Adjusting age MGMT status, associated poorer prognosis 0.66; 0.45–0.97; p = 0.033). Kyoto Encyclopedia Genes Genomes identified regulate involved cell cycle conclusion, biology is complex, but 4-miRNA pattern comprise promising biomarkers stratifying survivors.