Prognostic value of coexistence of abnormal expression of micro-RNA-200b and cyclic adenosine monophosphate-responsive element-binding protein 1 in human astrocytoma

• Published in: Human pathology 2014-10, Vol.45 (10), p.2154-2161
• Main Authors: Zhang, Jun-qing, MD, Yao, Qing-he, MD, PhD, Kuang, Yong-qin, MD, Ma, Yuan, MD, PhD, Yang, Li-bin, MD, PhD, Huang, Hai-dong, MD, PhD, Cheng, Jing-ming, MD, PhD, Yang, Tao, MD, PhD, Liu, En-yu, MD, PhD, Liang, Liang, MD, Fan, Ke-xia, MD, Zhao, Kai, MD, Xia, Xun, MD, PhD, Gu, Jian-wen, MD, PhD
• Format: Article
• Language: English
• Subjects: Adenosine; Aged; Astrocytoma; Astrocytoma - metabolism; Astrocytoma - mortality; Astrocytoma - pathology; Biomarkers, Tumor - analysis; Brain Neoplasms - metabolism; Brain Neoplasms - mortality; Brain Neoplasms - pathology; Confidence intervals; CREB-1; Cyclic AMP Response Element-Binding Protein - analysis; Cyclic AMP Response Element-Binding Protein - biosynthesis; Disease Progression; Female; Gene expression; Hospitals; Humans; Kaplan-Meier Estimate; Male; Medical prognosis; Micro-RNA-200b; MicroRNAs - analysis; MicroRNAs - biosynthesis; Middle Aged; Multivariate analysis; NMR; Nuclear magnetic resonance; Pathology; Prognosis; Real-Time Polymerase Chain Reaction; Regression analysis; Surgery; Tumor progression; Tumors
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2014.01.025

Summary Our aim was to investigate the expression of micro-RNA-200b (miR-200b) and cAMP-responsive element-binding protein 1 (CREB-1) in astrocytoma and its efficacy for predicting outcome. Both miR-200b and CREB-1 messenger RNA expression was measured in 122 astrocytomas and 30 nonneoplastic brain specimens by quantitative real-time polymerase chain reaction. Expression of miR-200b was significantly lower in astrocytoma than in nonneoplastic brain ( P < .001), whereas CREB-1 messenger RNA expression was significantly elevated in the tumors ( P < .001). Both miR-200b down-regulation and CREB-1 up-regulation were significantly associated with advanced pathologic grade ( P = .002 and P = .006, respectively). Low miR-200b expression correlated negatively with Karnofsky performance score ( P = .03), and high CREB-1 expression correlated positively with mean tumor diameter ( P = .03). By Kaplan-Meier analysis, low miR-200b, high CREB-1, and coexistence of abnormal miR-200b and CREB-1 expression (low miR-200b/high CREB-1) were predictive of shorter progression-free survival and overall survival in both grade III and grade IV astrocytoma. By multivariate analysis, only low miR-200b/high CREB-1 expression was an independent prognostic factor for poor prognosis in astrocytoma of advanced grade. Both miR-200b and CREB-1 may play important cooperative roles in the progression of human astrocytoma. The efficacy of miR-200b and CREB-1 together as a predictor of prognosis in astrocytoma patients is shown for the first time.