title: Up-regulation of microRNA-15b correlates with unfavorable prognosis and malignant progression of human glioma.
abstract: Recent studies have demonstrated that microRNA-15b (miR-15b) regulates cell cycle progression, proliferationnd apoptosis in glioma cells by targeting Cyclins. However, the clinical significance of miR-15b in human glioma remains unclear. Therefore, the aim of this study was to investigate the significance of miR-15b expression in diagnosis, prognosis and malignant progression of glioma. Quantitative real-time reverse transcriptive-PCR (qRT-PCR) was performed to examine miR-15b expression levels in 76 glioma tissues (13 grade II, 13 grade III and 50 grade IV gliomas) and seven glioma cell lines, as well as 10 non-neoplastic brain tissues and human astrocyte as control. MiR-15b showed significant increased expression in high-grade gliomas (P≤0.001) and glioma cells (fold change 2.8-7.6) relative to non-neoplastic brains and astrocyte, respectively. Additionally, high miR-15b expression was significantly associated with advanced WHO grade (P≤0.001), advanced patient age (P≤0.001) and low Karnofsky performance score (KPS, P≤0.001). Furthermore, Kaplan-Meier survival analysis and Cox regression analysis showed that patients with high miR-15b expression had significantly poor overall survival rate (P≤0.001) and miR-15b expression was an independent prognosis-predicting factor for glioma patients (P≤0.001; risk ratio=5.6), respectively. Moreover, miR-15b expression was examined in seven independent patients with primary grade II or III gliomas that spontaneously progressed to grade III or IV gliomas. Statistically significant higher expression (P=0.01) in the recurrent tumor compared with the corresponding primary tumor was observed in all of the seven patients. Our results suggest that miR-15b may be a prognostic predictor and be involved in malignant progression of glioma.
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of China Medical University Shenyang, Liaoning, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Pang
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of China Medical University Shenyang, Liaoning, P.R. China.
authors.forename: Yanlei
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Department of Neurosurgery, First Hospital of Qiqihar Qiqihar, Heilongjiang, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Department of Geriatric Medicine, First Affiliated Hospital of China Medical University Shenyang, Liaoning, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of China Medical University Shenyang, Liaoning, P.R. China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of China Medical University Shenyang, Liaoning, P.R. China.
authors.forename: Run
authors.initials: R
authors.lastname: Cui
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of China Medical University Shenyang, Liaoning, P.R. China.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of China Medical University Shenyang, Liaoning, P.R. China.
authors.forename: Yunjie
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000367:Age Factors; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D002460:Cell Line; D016009:Chi-Square Distribution; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D017567:Karnofsky Performance Status; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D016016:Proportional Hazards Models; D012307:Risk Factors; D015854:Up-Regulation
chemical_list: C505361:MIRN15 microRNA, human; D035683:MicroRNAs
keywords: glioma; malignant progression; miRNA-15b; microRNA; prognosis; up-regulation