Relationship Between Mutated Genes In Myelodysplastic Syndromes And Prognosis

Objective:To explore the relationship between gene mutation and main clinical features of patients with myelodysplastic syndrome and prognosis of patients.Through the analysis of the relationship between mutated genes and patient prognosis,the prognosis of patients can be more accurately judged,and through the analysis of the relationship between mutated genes and prognosis of patients after treatment with demethylating drugs,more individualized and favorable treatment can beformulated It can help clinically clarify the prognosis of patients and the next treatment.Methods:From May 2016 to May 2021,the outpatient and inpatient medical records of 215 patients who were diagnosed with myelodysplastic syndrome and underwent gene mutation screening in Sichuan Provincial People’s Hospital were retrospectively analyzed.Categorical variables were compared using the X2 test,quantitative data were compared using the Mann-Whitney U test,and prognostic factors were evaluated using binary logistic regression analysis,Kaplan-Meier,Log-rank test and Cox proportional hazards model.Results:1.Among 215 patients,108 patients who did not receive intensive treatment(decitabine,azacitidine or other demethylating drugs and bone marrow transplantation)were selected as the study for survival analysis object.The study found that in this group of patients,TP53 was the most frequently mutated gene(24%),followed by WT1(23%),ASXL1(15.7%),TET2(13%),DNMT3A(10%),RUNX1(8.3%),U2AF1(7.4%),SF3B1(4.6%),EZH2(4.6%),STAG2(4.6%).Univariate analysis showed that TP53 mutant wild-type patients had longer survival than TP53 mutant patients(median survival 13 months[95%CI,3.7-30 months]:median survival 4 months,[95%CI,1-5 months],P<0.01);U2AF1-mutant wild-type patients had a worse prognosis than U2AF1-mutant patients(median survival 8 months[95%CI,4-16 months]:Median survival 29 months[95%CI,NR],P=0.045);STAG2 mutant wild-type patients had shorter survival than STAG2 mutant patients(median survival 8 months[95%CI,3.7-16 months]:median survival 14 months[95%CI,NR],P=0.036).At the same time,univariate analysis also found that hemoglobin concentration(P=0.028),platelet count(P=0.020),complex karyotype(P<0.001),and IPSS-R risk stratification(P=0.001)were the main factors affecting the overall survival of MDS patients prognostic factors.In multivariate analysis,higher hemoglobin concentration(P=0.035)was found to be a good prognostic factor independent of other clinical features,while complex karyotype(P=0.04),presence of TP53 mutation(P=0.024)was a positive factor for MDS independent adverse prognostic factors in patients.2.Of the 215 patients,85 were treated with demethylating drugs.In this group of patients,the overall response rate was 40%,and in univariate analysis,TP53 mutation was a predictor of poor response rate(overall response rate was only 16.7%);None of the response rates had independent predictive value.The median survival of this cohort was 10 months,and univariate analysis found that hemoglobin concentration(P=0.038),complex karyotype(P<0.001),and IPSS-R stratification(P=0.012)remained significant factors for overall survival covariates,while TP53 mutation(P<0.001)was associated with worse prognosis,while STAG2 mutation(P=0.039)was associated with better prognosis.In multivariate analysis,TP53 mutation was identified as an independent covariate associated with worse overall survival.Conclusion:TP53 mutation is an independent poor prognostic factor in patients with myelodysplastic syndromes,and in TP53-mutated MDS patients,treatment with demethylating drugs is not effective.Analysis of the relationship between mutated genes and prognosis is helpful to predict the treatment effect of patients and formulate treatment strategies.