50岁年龄分组骨髓增生异常综合征患者基因突变分析及临床意义

Clinical significance and analysis of gene mutation in patients with myelodysplastie syndrome grouped by age 50

目的探讨50岁年龄分组骨髓增生异常综合征(MDS)患者基因突变特点及对预后的影响。方法纳入2015年1月至2024年3月江南大学附属医院、常州市第二人民医院确诊的MDS患者147例,采用二代测序技术靶向检测血液肿瘤相关基因,分析50岁年龄分组患者基因突变特点、基因突变与修订的国际预后积分系统(IPSS-R)的关系,以及对患者预后的影响。结果≤50岁MDS患者53例,>50岁患者94例。≤50岁组基因突变频率>20%的有RUNX1(37.7%)和ASXL1(24.5%),>50岁组为RUNX1(25.5%)、ASXL1(21.3%)、DNMT3A(21.3%)、TP53(20.2%)。SETBP1、WT1、PHF6基因在≤50岁组突变率较高(均P<0.05),SF3B1突变率在>50岁组较高(P=0.031)。SRSF2突变仅在>50岁组、CSMD1突变仅在≤50岁组检出(均P<0.05)。TP53突变易在IPSS-R高危及极高危组检出(P=0.028),ETV6、CSMD1(≤50岁组)及DDX41突变(>50岁组)则主要见于低、中危组(均P<0.05)。≤50岁MDS患者3年生存时间(OS)优于>50岁患者(P<0.001)。IDH1、NRAS、DNMT3A、SETBP1突变的>50岁患者3年OS比≤50岁突变患者更差(均P<0.05)。IPSS-R高危、极高危组≤50岁患者3年OS明显优于>50岁患者(均P<0.05)。多因素分析结果示年龄大于50岁,IPSS-R高危、极高危组以及IDH1和FLT3基因突变是患者预后不良的独立危险因素。结论两年龄组、不同IPSS-R分组间MDS患者基因突变谱存在差异,相同基因突变、IPSS-R高危组及极高危组50岁以上患者OS更差。年龄大于50岁,IPSS-R高危、极高危组以及IDH1和FLT3基因突变是影响患者预后的独立危险因素。

Objective To investigate the characteristics of gene mutations in patients with myelodysplastic syndrome(MDS)grouped by age 50 and the influence on prognosis.Methods The next-generation sequencing technology was used to detect the blood tumor-related genes in 147 MDS patients in the Affiliated Hospital of Jiangnan University and the second Hospital of Changzhou.The characteristics of gene mutations in patients grouped by age 50,and the relationship between gene mutations and the revised International Prognostic Score System(IPSS-R)was assessed,as well as the impact on patient prognosis.Results There were 53 MDS patients≤50 years old and 94 patients>50 years old.Mutation frequencies of RUNXI(37.7%)and ASXLI(24.5%)were>20%in≤50 years old group,and those of RUNXI(25.5%),ASXLI(21.3%),DNMT3A(21.3%)and TP53(20.2%)were>20%in>50 years old group.SETBP1,WT1,PHF6 mutation rates were higher in≤50 years old group(all P<0.05),whereas SF3BI mutation rates were higher in>50 years old group(P=0.031).SRSF2 mutations were only detected in>50 years old group,and CSMD1 mutations were only identified in≤50 years old group(both P<0.05).TP53 had a higher mutation rate in IPSS-R relatively high-risk group(P=0.028),while ETV6,CSMD1(≤50 years old)and DDX41(>50 years old)mutations were mainly found in relatively low-risk group(all P<0.05).The 3-year overall survival(OS)of MDS patients aged 50 years or younger was superior to that of patients over 50 years old(P<0.001).Patients with IDHI,NRAS,DNMT3A and SETBP1 mutations who were over 50 years old had worse 3-year OS than those aged 50 years or younger(all P<0.05).The 3-year OS of patients aged 50 years or younger in high-risk and very high-risk IPSS-R groups was significantly better than that of patients over 50 years old(all P<0.05).Multivariate analysis indicated that age over 50 years,IPSS-R high-risk group,very high-risk group and IDHI and FLT3 gene mutations were independent risk factors for poor prognosis.Conclusion There are differences in the gene mutation spectrum of MDS patients among the two age groups and different IPSS-R groups.Patients over 50 years old with the same gene mutation,IPSS-R high-risk or very high-risk group have poorer OS than those aged 50 years or younger.Older than 50 years,IPSS-R high-risk group,very high-risk group,IDHI and FLT3 gene mutations were independent risk factors affecting the prognosis of patients.