Prognostic value of SRSF2 mutations in patients with de novo myelodysplastic syndromes: A meta-analysis

BackgroundThe recent application of gene-sequencing technology has identified many new somatic mutations in patients with myelodysplastic syndromes (MDS). Among them, serine and arginine rich splicing factor 2 (SRSF2) mutations belonging to the RNA splicing pathway were of interest. Many studies have already reported the potential prognostic value of SRSF2 mutations in MDS patients, with controversial results. Therefore, a meta-analysis was performed to investigate their prognostic impact on MDS.MethodsDatabases, including PubMed, Embase and the Cochrane Library, were searched for relevant studies published up to 14 October 2016. Overall survival (OS) was selected as the primary endpoint, and acute myeloid leukemia (AML) transformation was the secondary endpoint. We extracted the corresponding hazard ratios (HRs) and their 95% confidence intervals (CIs) for OS and AML transformation from multivariate Cox proportional hazards models. The combined HRs with their 95% CIs were calculated using fixed or random effect models.ResultsA total of 10 cohort studies, covering 1864 patients with de novo MDS and 294 patients with SRSF2 mutations, were included in the final meta-analysis. Our results indicated that SRSF2 mutations had an adverse prognostic impact on OS (pSRSF2 mutations predicted a shorter OS (p = 0.009) and were more likely to transform to AML (p = 0.007).ConclusionsThis meta-analysis indicates an independent, adverse prognostic impact of SRSF2 mutations on OS and AML transformation in patients with de novo MDS. This also applies to the subgroup of low- or intermediate-1-IPSS risk MDS. The identification of mutations in SRSF2 can improve current risk stratification and help make treatment decisions.

研究背景
近年来，基因测序技术的应用在骨髓增生异常综合征（myelodysplastic syndromes, MDS）患者中发现了多种新的体细胞突变。其中，属于RNA剪接通路的丝氨酸精氨酸富集剪接因子2（serine and arginine rich splicing factor 2, SRSF2）突变备受关注。已有多项研究报道了SRSF2突变在骨髓增生异常综合征患者中的潜在预后价值，但所得结果尚存争议。为此，本研究开展一项荟萃分析，以探讨该突变对骨髓增生异常综合征患者的预后影响。

研究方法
本研究检索了PubMed、Embase及Cochrane图书馆数据库，搜集截至2016年10月14日发表的相关研究。以总生存期（overall survival, OS）为主要研究终点，急性髓系白血病（acute myeloid leukemia, AML）转化为次要研究终点。从多因素Cox比例风险模型中提取总生存期与急性髓系白血病转化的对应风险比（hazard ratios, HR）及其95%置信区间（confidence intervals, CI）。采用固定效应模型或随机效应模型计算合并后的风险比及其95%置信区间。

研究结果
最终共有10项队列研究纳入本荟萃分析，涵盖1864例初诊骨髓增生异常综合征患者及294例携带SRSF2突变的患者。本研究结果显示，SRSF2突变对总生存期具有不良预后影响：携带该突变的患者总生存期更短（p=0.009），且更易进展为急性髓系白血病（p=0.007）。

研究结论
本荟萃分析表明，SRSF2突变对初诊骨髓增生异常综合征患者的总生存期及急性髓系白血病转化具有独立的不良预后影响，该结论同样适用于IPSS风险分层为低危或中危-1的骨髓增生异常综合征亚组患者。检测SRSF2突变可优化当前的风险分层体系，辅助临床治疗决策的制定。