Prognostic value of U2AF1 mutant in patients with de novo myelodysplastic syndromes: a meta-analysis

被引:0
作者
Huifang Wang
Nanchen Zhang
Xia Wu
Xue Zheng
Yantao Ling
Yuping Gong
机构
[1] Sichuan University,Department of Hematology, West China Hospital
来源
Annals of Hematology | 2019年 / 98卷
关键词
Myelodysplastic syndromes; mutant; Prognostic value; Meta-analysis;
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摘要
U2 small nuclear RNA auxiliary factor 1 (U2AF1) mutant is the most common molecular biological abnormality in patients with myelodysplastic syndromes. Some studies have reported the prognostic impact of U2AF1 mutant in patients with de novo MDS, with discrepant results, so we do a meta-analysis about the relevant literatures to further investigate their prognostic impact on patients with de novo MDS. We conducted a literature search on databases such as PubMed, Embase, and the Cochrane Library to obtain studies on the prognosis of U2AF1 mutant in patients with de novo MDS published up to August 9, 2018. The primary endpoint was overall survival (OS), and the secondary endpoint was acute myeloid leukemia (AML) transformation. We extracted the hazard ratios (HRs) of OS and AML transformation and their 95% confidence intervals (CIs). Meta-analysis was performed by selecting a fixed-effect model or a random-effects model based on the heterogeneity between studies. A total of 14 cohort studies were included in the final meta-analysis, including 3322 patients with de no MDS, in which 390 patients were associated with U2AF1 mutant. The results showed that U2AF1 mutant had an adverse prognostic impact on OS (HR = 1.84, 95% CI: 1.45-2.33, P < 0.00001) and AML transformation (HR = 2.47, 95% CI: 1.50-4.06, P = 0.0004). U2AF1 mutant was associated with shorter OS in subgroup analyses of low- or intermediate-1-IPSS, U2AF1S34 and U2AF1Q157/R156. Out meta-analysis indicates that U2AF1 mutants are independent, detrimental prognostic factors for OS and AML transformation in patients with de novo MDS, as well as associating with shorter OS in subgroups of low- or intermediate-1-IPSS, U2AF1S34 and U2AF1Q157/R156. Further prospective studies are needed in the future, and subgroup analysis of U2AF1 subgroups is needed to obtain a more reliable basis for the impact of U2AF1 mutant on the prognosis of de novo MDS.
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页码:2629 / 2639
页数:10
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  • [1] Begg CB(1994)Operating characteristics of a rank correlation test for publication bias Biometrics 50 1088-1101
  • [2] Mazumdar M(2012)Validation of a prognostic model and the impact of mutations in patients with lower-risk myelodysplastic syndromes J Clin Oncol 30 3376-3382
  • [3] Bejar R(2014)The role of splicing factor mutations in the pathogenesis of the myelodysplastic syndromes Adv Biol Regul 54 153-161
  • [4] Stevenson KE(2014)A pan-cancer analysis of transcriptome changes associated with somatic mutations in U2AF1 reveals commonly altered splicing events PLoS One 9 e87361-3218
  • [5] Caughey BA(2012)Mutations affecting mRNA splicing define distinct clinical phenotypes and correlate with patient outcome in myelodysplastic syndromes Blood 119 3211-634
  • [6] Abdel-Wahab O(1997)Bias in meta-analysis detected by a simple, graphical test BMJ 315 629-697
  • [7] Steensma DP(2018)Mutations and prognosis in myelodysplastic syndromes: karyotype-adjusted analysis of targeted sequencing in 300 consecutive cases and development of a genetic risk model Am J Hematol 93 691-62
  • [8] Galili N(2016)Mutations of myelodysplastic syndromes (MDS): an update Mutat Res Rev Mutat Res 769 47-57
  • [9] Raza A(2011)Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes Nat Genet 44 53-3089
  • [10] Kantarjian H(2015)Mutations in the spliceosomal machinery genes SRSF2, U2AF1, and ZRSR2 and response to decitabine in myelodysplastic syndrome Anticancer Res 35 3081-26