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
- VernacularTitle:骨髓增殖性肿瘤患者血清金属蛋白酶抑制剂-1、基质金属蛋白酶-9、血管内皮生长因子与骨髓纤维化程度的相关性
- Author:
Ling SUN
1
;
Tantan LI
;
Xifeng WU
;
Lijie MEN
;
Meiyan JIA
;
Jun LU
Author Information
- Publication Type:Research Article
- Keywords: myeloproliferative neoplasms; myelofibrosis; vascular endothelial growth factor; matrix metalloproteinase-9; tissue inhibitor of metalloproteinases-1; extracellular matrix; collagen deposition
- From: Journal of Clinical Medicine in Practice 2024;28(11):34-40
- CountryChina
- Language:Chinese
-
Abstract:
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 patients 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 alone 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; theAUC 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 ofAUC 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; theAUC 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 indicators can predict the MF degree of MPN patients.
