NGS In Evaluating MDS Disease Heterogeneity And Guide The Value Of The Treatment And Prognosis

Objective:The second-generation sequencing technology(NGS)was used to detect gene mutations in 73 patients with confirmed myelodysplastic syndrome(MDS),to evaluate the heterogeneity of the disease and analyze and conclude the role of related gene mutations in guiding treatment and prognosis.Methods:In this study,73 patients with MDS who received second-generation sequencing for gene mutation were admitted to First Affiliated Hospital of University of Science and Technology of China(Anhui Provincial Hospital)from April 2016 to June 2022.General clinical characteristics(gender,age,neutrophilic count,platelet count,hemoglobin content,etc.)were collected at the time of initial diagnosis.And its gene mutation,WHO(2016)typing,IPSS-R risk score,survival time and survival state,etc.The general clinical characteristics of 73 patients with MDS were described,and the differences of gene mutation frequency in gender,age,classification and risk stratification were analyzed and summarized.The influences of general clinical features and gene mutations on prognosis and survival time of MDS patients were analyzed,and univariate and multivariate analyses were conducted on each factor affecting prognosis.Results:1.Mutation gene frequency:in the 73 routine of the MDS,which tested gene mutations,there were 29 genetic mutations.among which 58 patients(79.5%)had at least one gene mutation,22 patients(30.14%)had only one gene mutation,16 patients(21.92%)had two gene mutations,and 20 patients(27.40%)had three or more gene mutations.No mutation was detected in 15 patients(20.5%).Among them,the mutation frequencies greater than 5%are:ASXL1(27.4%),TP53(23.3%),TET2(23.3%),U2AF1(20.5%),DNMT3A(9.6%),SF3B1(9.6%),SRSF2(8.2%),RUNX1(8.2%),IDH1(5.5%),ETV6(5.5%).And WT1(5.5%).2.Frequency distribution characteristics of mutant genes:(1)Among 73 patients with MDS,according to WHO(2016)classification,the most common mutant gene in MDSMLD was ASXL 1(9.6%);The most common mutated gene in MDS-RS was SF3B 1(5.5%).The most common mutated gene in MDS-EB-1 was TP53(9.6%).The most common mutated gene in MDS-EB-2 was ASXL 1(9.6%).The most common mutated gene in MDS-U was ASXL 1(2.7%).No MDS-SLD cases were included.(2)In the prognosis stratification of IPSS-R,the highest frequency of mutant genes was TET2(6.8%)in the low-risk group,TET2(9.6%)in the middle-risk group,TP53(9.6%)in the high-risk group,and TP53(4.1%)in the extremely high-risk group.(3)Functional classification of each mutant gene was conducted according to the number of mutation cases and mutation frequency from high to low as follows:Epigenetic modification(58/73,79.5%),RNA shear factors(29/73,39.7%),DNA damage and repair(20/73,27.4%),transcription factors(19/73,26.0%),and signal transduction(12/73,16.4%).3.The relationship between gene mutation and clinical features:(1)The mutation of TP53(P=0.030),TET2(P<0.001),SRSF2(P=0.027),etc.,had a high incidence in elderly patients with MDS.(2)There were significant differences in the distribution of DNMT3A(P=0.016),SF3B1(P=0.002),IDH1(P=0.025),WT1(P=0.025)among all WHO types(P<0.05).(3)The mutant genes of ASXL1,TP53,TET2,U2AF1,DNMT3A,SF3B1 and SRSF2 appeared in all risk groups.The low-risk group had no ETV6 mutant gene,and the extremely high-risk group had no RUNX1,IDH1 and WT1 mutant genes.No significant difference was found between mutation frequency and risk stratification(P>0.05).4.Survival analysis of prognostic factors:(1)We conducted prognostic analysis of single gene mutations and found that TP53 mutations were significantly associated with poor prognosis,while remaining gene mutations were not associated with prognosis.(2)Among 73 patients with MDS,the mutation frequency of ASXL1 was the highest.In the case of ASXL1 mutation,the co-mutation frequency of TET2 and U2AF1 was the highest.The prognosis analysis of ASXL1 mutation combined with TET2 and U2AF1 mutation was conducted respectively.There was no significant difference in survival time between comutant genes and non-comutant genes(P>0.05).(3)Univariate survival analysis was performed on 73 patients with MDS,and the results showed:Gender,age≥60 years old,newly diagnosed hemoglobin content<80g/L,newly diagnosed bone marrow primitive cell proportion≥5%,accompanied by CD34,CD117,CD13,HLA-DR,CD33,CD38 immunophenotypes,and poor prognosis karyotype were all adverse prognostic factors for overall survival of patients.Multivariate Cox regression analysis of single factor index showed that gender,age≥60 years old and TP53 gene mutation were independent risk factors for poor prognosis in overall survival(P<0.05).Conclusions:1.79.5%of MDS patients had at least one or more gene mutations,and the mutation frequency was ASXL1,TP53,TET2,U2AF1,DNMT3A,SF3B1,SRSF2,RUNX1,IDH1,ETV6,WT1.2.The genetic mutation distribution of MDS patients is related to the characteristics of age,WHO(2016).3.Sex,Age≥ 60 years,and TP 53 mutations were all independent risk factors for poor overall survival(P<0.05).4.Based on the data of 73 patients with MDS in a single center,this study evaluated and analyzed the clinical characteristics of patients and performed prognostic correlation analysis by NGS,providing evidence-based medical evidence for clinical guidance of differentiated treatment of MDS.