The prognostic significance of global aberrant alternative splicing in patients with myelodysplastic syndrome
Journal
Blood Cancer Journal
Journal Volume
8
Journal Issue
8
Date Issued
2018
Author(s)
Chiu, Y.-C.
Kao, C.-J.
Tseng, M.-H.
Abstract
Aberrant alternative splicing (AS) is a hallmark of cancer development. However, there are limited data regarding its clinical implications in myelodysplastic syndrome (MDS). In this study, we performed an in-depth analysis of global AS in 176 primary MDS patients with 20 normal marrow transplant donors as reference. We found that 26.9% of the expressed genes genome-wide were aberrantly spliced in MDS patients compared with normal donors. These aberrant AS genes were related to pathways involved in cell proliferation, cell adhesion and protein degradation. A higher degree of global aberrant AS was associated with male gender and U2AF1 mutation, and predicted shorter overall survival and time to leukemic change. Moreover, it was an independent unfavorable prognostic factor irrespective of age, revised international prognostic scoring system (IPSS-R) risk, and mutations in SRSF2, ZRSR2, ASXL1, TP53, and EZH2. With LASSO-Cox regression method, we constructed a simple prognosis prediction model composed of 13 aberrant AS genes, and demonstrated that it could well stratify MDS patients into distinct risk groups. To our knowledge, this is the first report demonstrating significant prognostic impacts of aberrant splicing on MDS patients. Further prospective studies in larger cohorts are needed to confirm our observations. ? 2018, The Author(s).
SDGs
Other Subjects
protein p53; transcription factor EZH2; biological marker; transcriptome; adult; aged; alternative RNA splicing; Article; ASXL1 gene; cell adhesion; cell proliferation; controlled study; female; gender; gene; gene expression; gene mutation; human; International Prognostic Scoring System; major clinical study; male; myelodysplastic syndrome; overall survival; prognosis; protein degradation; SRSF2 gene; U2AF1 gene; ZRSR2 gene; biology; gene expression profiling; genetics; Kaplan Meier method; middle aged; mortality; myelodysplastic syndrome; procedures; prognosis; proportional hazards model; reproducibility; very elderly; Aged; Aged, 80 and over; Alternative Splicing; Biomarkers; Computational Biology; Female; Gene Expression Profiling; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myelodysplastic Syndromes; Prognosis; Proportional Hazards Models; Reproducibility of Results; Transcriptome
Publisher
Nature Publishing Group
Type
journal article