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

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.