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

SUN Ling; LI Tantan; WU Xifeng; MEN Lijie; JIA Meiyan; LU Jun

doi:10.7619/jcmp.20234037

Journal of Clinical Medicine in Practice > 2024 > 28(11): 34-40. > DOI: 10.7619/jcmp.20234037

SUN Ling, LI Tantan, WU Xifeng, MEN Lijie, JIA Meiyan, LU Jun. 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[J]. Journal of Clinical Medicine in Practice, 2024, 28(11): 34-40. DOI: 10.7619/jcmp.20234037

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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

Department of Hematology, Ji'nan City People's Hospital in Shandong Province, Ji'nan, Shandong, 271199

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Received Date: December 12, 2023
Revised Date: March 11, 2024
Available Online: June 17, 2024

Graphical Abstract

Abstract

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; 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 indicators can predict the MF degree of MPN patients.

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References (26)

References

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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

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