Clinical Characteristics And Prognosis Of Myelodysplastic Syndromes Based On NGS Technology

BackgroundMyelodysplastic syndromes（MDS）are myeloid hematological malignancies with high risk of transformation to acute myeloid leukemia（AML）,also known as pre-leukemia,with a very poor prognosis.Several studies have shown that about 70-90%of MDS patients have one or more gene mutations,and gene mutations play a key role in the new era of personalized medicine for MDS.With the rapid development of Next Generation Sequencing（NGS）,it is undeniable that more and more mutated genes have been detected in MDS patients.Therefore,based on next-generation sequencing technology,this study analyzed the genetic mutations and clinical data of MDS patients,and aimed to explore the correlation between genetic mutations and clinical characteristics and prognosis.ObjectiveUsing NGS to detect mutated genes,to explore the correlation of gene mutation characteristics with clinical factors and prognosis,in order to accurately diagnose MDS,optimize disease progression monitoring,and guide clinical medication strategies.Methods1.Collect the clinical data of 222 MDS patients who were treated in Luoyang Central Hospital and the First Affiliated Hospital of Zhengzhou University（January 2015December 2020）.2.First,the correlation between gene mutation and clinical characteristics and prognosis of 141 MDS patients detected by next-generation sequencing technology was analyzed,and TET2 gene,with the highest mutation rate in this study,was found.3.Secondly,we further analyzed the relationship between clinical characteristics and prognosis of TET2 mutant group and wild group.4.Finally,using the clinical data of another 81 patients,univariate and multivariate analysis were conducted to further verify the prognostic factors of MDS patients.Results1.A total of 29 gene mutations were detected in 141 MDS patients,90.07%（127/141 cases）of the patients carried at least one gene mutation,of which 28.37%（40/141 cases）had one gene mutation,and 61.70%had two or more mutations.Mutations in more than 2 genes.TET2 was the gene with the highest mutation rate,with a mutation rate of 49.65%（70/141 cases）.2.According to the function of mutated genes detected in MDS patients,the mutation frequency is in order:epigenetic-related genes（70.92%）,splicing-related genes（41.13%）,transcriptional regulation-related genes（19.86%）,and cell proliferation and apoptosis related genes（19.15%）,signal transduction-related genes（18.44%）.3.The research on partner genes found that only the WT1 gene had the same mutation rate as the single mutation rate,and the other mutated genes had the accompanying mutation rate>the single mutation rate（P<0.0001）.4.The mutation rates of U2AF1,SETBP1 and JAK2 were significantly different between patients with normal karyotype and abnormal karyotype（P1=0.009,P2=0.008,P3=0.035）.U2AF1 mutation was closely associated with abnormal karyotype[P=0.009,OR=0.35（95%CI 0.15～0.79）].SETBP1 was closely associated with abnormal karyotype[P=0.008,OR=0.15（95%CI 0.03～0.63）].JAK2 mutation was closely associated with normal karyotype[P=0.035,OR=0.00（95%CI 0.00～0.89）].5.There was a statistically significant difference in the proportion of ASXL1 mutation among the four blood groups（χ2=9.178,P=0.027）.The patients with ETV6 mutation gene were all younger than 60 years old（P=0.008）.6.According to the number of gene mutations,the patients were divided into 0-2 gene mutation group with 88 cases（62.41%）and 3 or more gene mutation group with 53 cases（37.59%）.The difference in OS between the two groups was statistically significant（χ2=3.887,P=0.0487）.7.We analyzed and compared the differences between TET2 mutant group and wild group from gender,age,laboratory examinations（the total of WBC,the absolute value of neutrophil cell,the total of hemoglobins and platelets）,proportion of bone marrow primordial cells,IPSS-R risk classification,WHO classification,cytogenetics,chromosome and chromosome karyotype abnormality detection rate.The results showed that only hemoglobin difference was statistically significant（P=0.039）,and there was no significant difference in other items.8.According to whether there is TET2 mutation or not,there are 70 patients in TET2 mutation group（49.65%）and 71 patients in wild group（50.35%）.The study found that the number of gene mutations in TET2 mutation group is 2.74 ± 1.37,and the number of gene mutations in wild group is 1.65±1.50.The difference is statistically significant（P=0.000,t=-4.520）.The difference of OS between the two groups is also statistically significant（x 2=8.206,P=0.0042）.9.Using the data of 81 patients,through univariate and multivariate analysis,it was found that the number of gene mutations≥3 was an independent risk factor affecting MDS patients（P<0.05）.Conclusions1.90.07%of MDS patients carry at least one gene mutation,and 61.7%of patients have intergenic concomitant mutations.As the number of gene mutations increases,the prognosis of patients may be worse.2.MDS patients with TET2 mutation have poor prognosis,patients with U2AF1 mutation are not found to have poor prognosis,and patients with TET2-U2AF1 co-mutation have poor prognosis.3.Gene mutation characteristics may be related to clinical factors such as MDS subtype,IPSS-R risk,karyotype,patient age and prognosis.