Prognostic alternative mRNA splicing signatures and associated splicing factors in acute myeloid leukemia
| العنوان: | Prognostic alternative mRNA splicing signatures and associated splicing factors in acute myeloid leukemia |
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| المؤلفون: | Kankan Wang, Wei Zhang, Peng Jin, Junmin Li, Yun Tan |
| المصدر: | Neoplasia: An International Journal for Oncology Research, Vol 22, Iss 9, Pp 447-457 (2020) Neoplasia (New York, N.Y.) |
| بيانات النشر: | Elsevier BV, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, Cancer Research, RBSURV, robust likelihood-based survival modeling, European LeukemiaNet, Exon, 0302 clinical medicine, hemic and lymphatic diseases, Gene expression, A5SS, Alternative 5′ splice site, AS, Alternative splicing, Myeloid leukemia, Prognosis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, MXE, Mutually exclusive exons, Leukemia, Myeloid, Acute, 030220 oncology & carcinogenesis, RNA splicing, PSI, Percent spliced in, RNA Splicing Factors, Original article, medicine.medical_specialty, SE, Skipped exon, A3SS, Alternative 3′ splice site, ROC, Receiver operating characteristic, lcsh:RC254-282, HR, Hazard ratio, OS, overall survival, RI, Retained intron, 03 medical and health sciences, Splicing factor, CRISPR, Clustered regularly interspaced short palindromic repeats, Internal medicine, Biomarkers, Tumor, medicine, Humans, RBM39, RNA Binding Motif Protein 39, RNA, Messenger, SETD5, SET Domain Containing 5, Acute myeloid leukemia, business.industry, Mechanism (biology), Gene Expression Profiling, Alternative splicing, AUC, Area under the curve, 030104 developmental biology, ELN, European Leukemia Net, AML, Acute myeloid leukemia, TCGA, The Cancer Genome Atlas, Transcriptome, business |
| الوصف: | The dysregulation of alternative splicing (AS) has emerged as a mechanism of acute myeloid leukemia (AML). However, the prognostic impact of AS events remains under-explored in AML. Here we report the prognostic value of AS events and associated splicing factors based on three datasets of AML patients. We defined the landscape of AS events in AML and identified 7033 AS events associated with the survival of AML patients. Based on these events, we further developed a composite 15 AS event-based prognostic signature, which was independent of the cytogenetic risk stratification and patient age, and showed a better performance than known gene expression signatures. More importantly, our new signature markedly improved the European LeukemiaNet (ELN) risk classification, indicating a broad applicability in the clinical management of AML. Furthermore, the splicing-regulatory network established the correlations between prognostic AS events and associated splicing factors. The finding was validated by CRISPR-based data, which indicated that the increased expression of RBM39 contributed to the higher exon inclusion of SETD5 and conferred a poor outcome. Together, AS events may serve as a novel assortment of prognosticators for AML and could refine the ELN risk stratification. The splicing regulatory network provides clues regarding the splicing factor-mediated mechanisms of AML. |
| تدمد: | 1476-5586 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1277e66e4646bc171b7371c6de2a9dd9Test https://doi.org/10.1016/j.neo.2020.06.004Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1277e66e4646bc171b7371c6de2a9dd9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765586 |
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