Role of p15(INK4B) Methylation in Patients With Myelodysplastic Syndromes: A Systematic Meta-Analysis |
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| Institution: | 1. Department of Hematology, Oncology, and Rheumatology, University Hospital of Heidelberg, Heidelberg, Germany;2. Department of Hematology and Oncology, Cedars-Sinai Outpatient Cancer Center, Los Angeles, CA;3. Department of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany;4. Department of Hematology and Oncology, National Center of Tumor Diseases, Heidelberg, Germany;1. Departamento de Cardiología, Hospital del Mar, Grupo de Investigación Biomédica en Enfermedades del Corazón, IMIM (Instituto Hospital del Mar de Investigaciones Médicas), Universitat Autònoma de Barcelona, Barcelona, España;2. Departamento de Cardiología, Hospital del Mar, Barcelona, España;3. Laboratorio de Referencia de Catalunya, El Prat de Llobregat, Barcelona, España;4. Grupo de Investigación en Genética y Epidemiología Cardiovascular, Programa de Investigación en Procesos Inflamatorios y Cardiovasculares, IMIM (Instituto Hospital del Mar de Investigaciones Médicas)-Hospital del Mar, Barcelona, España;1. Wiser Healthcare, Sydney School of Public Health, The University of Sydney, NSW, 2006, Australia;2. School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Sydney, NSW, 2052, Australia;3. Sydney School of Public Health, The University of Sydney, NSW, 2006, Australia;4. Sydney Medical School – Westmead, The University of Sydney, Westmead, NSW, 2145, Australia;5. Westmead Breast Cancer Institute, Westmead Hospital, Westmead, NSW, Australia;1. Department of Medicine A, Hematology, Oncology and Pneumology, University of Münster, Münster, Germany;2. Institute of Medical Informatics, University of Münster, Münster, Germany;3. Biotech Research and Innovation Centre and Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark;4. Genetic Epidemiology of Vascular Disorders, Leibniz-Institute for Arteriosclerosis Research at the University of Münster, Münster, Germany;5. III Medizinische Klinik, Department of Hematology and Oncology, Medical Faculty Mannheim of the University of Heidelberg, Heidelberg, Germany;6. Institute of Transfusion Medicine and Transplantation Immunology, University of Münster, Münster, Germany;7. Institute for Molecular Tumor Biology, University of Münster, Münster, Germany |
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| Abstract: | BackgroundTumor suppressor gene cyclin-dependent kinase inhibitor 2B (p15(INK4B)) methylation has been frequently reported in myelodysplastic syndromes (MDS). However, the association between p15(INK4B) methylation and MDS remains elusive. Thus, this meta-analysis was first conducted to evaluate the clinical significance of p15(INK4B) methylation in MDS.Materials and MethodsEligible studies were identified via an online electronic databases search. The overall odds ratios (ORs) or hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated.ResultsTwenty-eight studies published between 1997 and 2017 were identified, including 1205 MDS patients and 243 nontumor controls. No evidence of heterogeneity was found in our study. p15(INK4B) methylation was significantly elevated in MDS compared with nontumor controls (OR, 10.37; P < .001). In addition, p15(INK4B) methylation was significantly higher in advanced MDS than in early MDS (OR, 4.70; P < .001) and was linked to an unfavorable overall survival (multivariate analysis: HR, 1.78; 95% CI, 1.23-2.71). Subgroup analyses on the basis of ethnicity and detection method showed that the results remained significant in different subgroups (all Ps < .05).ConclusionOur findings suggest that p15(INK4B) methylation might play an important role in the development, progression, and poor prognosis of MDS. More prospective studies with larger study populations are needed. |
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| Keywords: | Development MDS Methylation Prognosis Progression |
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