High expression of RUNX1 is associated with poorer outcomes in cytogenetically normal acute myeloid leukemia
| Autor: | Xiaoyan Ke, Hongmei Jing, Huaping Fu, Jing Wang, Jinlong Shi, Kai Hu, Lei Tian, Keman Xu, Ji-Jun Wang, Lin Fu |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine RUNX1 Adolescent Microarray Kaplan-Meier Estimate CN-AML Bioinformatics Disease-Free Survival law.invention Young Adult 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Text mining law hemic and lymphatic diseases microRNA Biomarkers Tumor medicine Humans prognostic biomarker Gene Aged business.industry Middle Aged Prognosis medicine.disease Leukemia Myeloid Acute Leukemia 030104 developmental biology Oncology chemistry 030220 oncology & carcinogenesis Core Binding Factor Alpha 2 Subunit embryonic structures Cohort Cancer research Suppressor Female business Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.7489 |
| Popis: | Depending on its expression level, RUNX1 can act as a tumor promoter or suppressor in hematological malignancies. The clinical impact of RUNX1 expression in cytogenetically normal acute myeloid leukemia (CN-AML) remained unknown, however. We evaluated the prognostic significance of RUNX1 expression using several public microarray datasets. In the testing group (n = 157), high RUNX1 expression (RUNX1high) was associated with poorer overall survival (OS; P = 0.0025) and event-free survival (EFS; P = 0.0025) than low RUNX1 expression (RUNX1low). In addition, the prognostic significance of RUNX1 was confirmed using European Leukemia Net (ELN) genetic categories and multivariable analysis, which was further validated using a second independent CN-AML cohort (n = 162, OS; P = 0.03953). To better understand the mechanisms of RUNX1, we investigated genome-wide gene/microRNAs expression signatures and cell signaling pathways associated with RUNX1 expression status. Several known oncogenes/oncogenic microRNAs and cell signaling pathways were all up-regulated, while some anti-oncogenes and molecules of immune activation were down-regulated in RUNX1high CN-AML patients. These findings suggest RUNX1high is a prognostic biomarker of unfavorable outcome in CN-AML, which is supported by the distinctive gene/microRNA signatures and cell signaling pathways. |
| Databáze: | OpenAIRE |
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