Image_3_A Novel Scoring System for Risk Assessment of Elderly Patients With Cytogenetically Normal Acute Myeloid Leukemia Based on Expression of Three AQP1 DNA Methylation-Associated Genes.TIF
Background: Aquaporin 1 (AQP-1), a transmembrane water channel protein, has been proven to involve in many diseases' progression and prognosis. This research aims to explore the prognostic value of AQP-1 in elderly cytogenetically normal acute myeloid leukemia (CN-AML).
Methods: Complete clinical and expression data of 226 elderly patients (aged > 60) with cytogenetically normal acute myeloid leukemia (CN-AML) were downloaded from the databases of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). We have explored prognostic significance of AQP-1, investigated the underlying mechanism, and developed a novel scoring system for the risk assessment of elderly patients with AML based on AQP1 methylation.
Results: In the first and second independent group, AQP1 shows lower expression in CN-AML than normal people, while high AQP1 expression and AQP1 promoter hypomethylation were related to better overall survival (OS; P < 0.05). To understand the underlying mechanisms, we investigated differentially expressed genes (DEGs), miRNA and lncRNA associated with AQP1 methylation. A three-gene prognostic signature based on AQP1 methylation which was highly correlated with OS was established, and the performance was validated by Permutation Test and Leave-one-out Cross Validation method. Furthermore, an independent cohort was used to verify the prognostic value of this model.
Conclusions: AQP1 methylation could serve as an independent prognostic biomarker in elderly CN-AML, and may provide new insights for the diagnosis and treatment for elderly CN-AML patients.
History
References
- https://doi.org//10.1002/hon.2046
- https://doi.org//10.1001/jamaoncol.2014.161
- https://doi.org//10.1182/blood-2005-01-0178
- https://doi.org//10.1182/asheducation-2004.1.98
- https://doi.org//10.1038/sj.leu.2404004
- https://doi.org//10.1016/S0268-960X(03)00040-7
- https://doi.org//10.1182/blood-2016-01-693879
- https://doi.org//10.3322/caac.20085
- https://doi.org//10.1186/1756-8722-6-57
- https://doi.org//10.1038/nm.4125
- https://doi.org//10.1159/000133639
- https://doi.org//10.3892/ol.2018.7727
- https://doi.org//10.1093/abbs/gmy023
- https://doi.org//10.3892/ol.2018.8170
- https://doi.org//10.1080/08923973.2017.1417998
- https://doi.org//10.1016/j.biopha.2018.06.048
- https://doi.org//10.1002/cbin.10102
- https://doi.org//10.3892/mmr.2018.9198
- https://doi.org//10.1039/C5MB00347D
- https://doi.org//10.1177/0194599814521569
- https://doi.org//10.1096/fj.14-260828
- https://doi.org//10.1016/j.juro.2010.09.081
- https://doi.org//10.1002/jcp.25726
- https://doi.org//10.1002/ijc.31609
- https://doi.org//10.1016/j.febslet.2007.04.059
- https://doi.org//10.1038/oncsis.2016.77
- https://doi.org//10.1016/j.cell.2009.10.023
- https://doi.org//10.1016/B978-0-12-396456-4.00009-2
- https://doi.org//10.1164/rccm.201703-0660OC
- https://doi.org//10.1242/jcs.119347
- https://doi.org//10.1038/nm.4424
- https://doi.org//10.3389/fgene.2016.00037
- https://doi.org//10.1111/hepr.13220
- https://doi.org//10.1038/s41598-017-00327-0
- https://doi.org//10.1007/s13577-018-0206-1
- https://doi.org//10.3892/mmr.2018.9279
- https://doi.org//10.3892/ol.2018.8088
- https://doi.org//10.1016/j.bbrc.2018.06.007
- https://doi.org//10.1186/gb-2013-14-9-r105
- https://doi.org//10.1182/blood-2016-08-733196
- https://doi.org//10.1002/ajh.23848
- https://doi.org//10.1200/JCO.2014.55.1564
- https://doi.org//10.1038/leu.2016.65
- https://doi.org//10.1016/S0140-6736(10)62105-8
- https://doi.org//10.18632/oncotarget.3024
- https://doi.org//10.18632/oncotarget.6226
- https://doi.org//10.1098/rsfs.2017.0066
- https://doi.org//10.1038/s41375-018-0070-8
- https://doi.org//10.1186/s13148-019-0776-0
- https://doi.org//10.1042/BST0320910
- https://doi.org//10.1016/S1470-2045(17)30576-4
- https://doi.org//10.1016/j.cbpa.2018.03.003
- https://doi.org//10.1016/j.resp.2019.04.005
- https://doi.org//10.1016/j.eururo.2008.10.014
- https://doi.org//10.1182/blood-2005-05-2164
- https://doi.org//10.1016/j.jare.2019.05.006
- https://doi.org//10.1182/blood-2005-02-0560