Correlations of serum tissue inhibitor of metalloproteinases-1,matrix metalloproteinase-9 and vascular endothelial growth factor with degree of myelofibrosis in patients with myeloproliferative neoplasms
Objective To explore the correlations of serum vascular endothelial growth factor(VEGF),matrix metalloproteinase-9(MMP-9)and tissue inhibitor of metalloproteinases-1(TIMP-1)with grading of myelofibrosis(MF)in patients with myeloproliferative neoplasms(MPN).Methods Ninety patients with Philadelphia chromosome negative(Ph-)MPN were selected as MPN group.According to the grading criteria for myelofibrosis by the World Health Organization(WHO)in 2016,MPN pa-tients were divided into pre-fibrosis or early fibrosis group with 54 cases and significant fibrosis group with 36 cases;another 50 healthy volunteers were selected as the control group.Levels of serum VEGF,MMP-9 and TIMP-1 were detected by enzyme-linked immunosorbent assay,and the ratio of TIMP-1 to MMP-9(TIMP-1/MMP-9)was calculated.Spearman rank correlation test was used to analyze the correlations of VEGF,MMP-9,TIMP-1 and TIMP-1/MMP-9 with MF grading.Receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of each indicator a-lone or their combination for diagnosing MPN or distinguishing MF grading.Results Compared with the control group,the serum levels of VEGF,MMP-9 and TIMP-1 in the MPN group increased significantly(P＜0.05).Values of area under the curve(AUC)of VEGF,MMP-9,TIMP-1 and TIMP-1/MMP-9 for diagnosing MPN were 0,834,0.745,0.923 and 0.618 respectively;the AUC of the combined diagnosis of MPN by VEGF,MMP-9 and TIMP-1 was 0.960;when the optimal cut-off value was 0.627,the sensitivity was 85.56％,and the specificity was 92.00％.Compared with the pre-fibrosis or early fibrosis group,the serum levels of VEGF,TIMP-1 and TIMP-1/MMP-9 in the significant fibrosis group increased significantly(P＜0.05).Spearman correlation analysis showed that VEGF(r=0.378,P=0.001),TIMP-1(r=0.512,P＜0.001)and TIMP-1/MMP-9(r=0.353,P=0.001)were positively correlated with the MF grading of MPN patients(P＜0.05).ROC curve analysis showed that the values of AUC of VEGF,MMP-9,TIMP-1 and TIMP-1/MMP-9 for distinguishing patients with pre-fibrosis or early fibrosis from those with significant fibrosis were 0.723,0.523,0.802 and 0.708 respectively;the AUC of the combined detection of VEGF,TIMP-1 and TIMP-1/MMP-9 for distinguishing patients with pre-fibrosis or early fibrosis from those with significant fibrosis was 0.838;when the optimal cut-off value was 0.530,the sensitivity was 72.22％,and the specificity was 85.19％.Conclusion Serum VEGF,TIMP-1 and TIMP-1/MMP-9 can reflect the MF progression of MPN patients,and the combined detection of these indica-tors can predict the MF degree of MPN patients.
万方数据
维普
