AML-226 A Prospective Study to Evaluate the Prognostic Implications of MMP-2 Gene in Acute Myeloid Leukemia

Abstract

Context Acute myeloid leukemia (AML) is a complex hematologic malignancy characterized by the uncontrolled proliferation of immature myeloid cells in the bone marrow. Matrix metalloproteinase-2 (MMP-2) gene has been involved in tumor invasion and trafficking of normal hematopoietic cells. However, the molecular mechanism of MMP-2 and the molecular interaction in AML remains unknown. Objective In this study, we aimed to characterize the molecular functions, clinical and prognostic value of MMP-2 gene in AML. Design and Setting Prospective clinical research Methods In this study, we investigated the expression level of the MMP-2 gene in AML (n=173) and control (n=70) cases. Then, we did correlation analysis to find the potentially associated gene linked with the MMP-2 gene based on their expression levels using UALCAN database. Kaplan–Meier survival estimation was performed to evaluate the prognostic significance of MMP-2 using Kaplan Meier plotter. In addition, we assessed the DNA methylation status of MMP-2 gene using MEXPRESS database. Moreover, we also explored the molecular mechanisms of MMP-2 in AML by performing gene set enrichment analysis (GSEA) analysis. Finally, the relationship of MMP-2 expression with different functional states was studied using SANGER Box 3.0 database. Results In our analyses, MMP-2 mRNA was significantly overexpressed in AML (n=173) cohorts as compared with normal cases (n=70) and closely associated with poor overall survival (P <0.05). In correlation analysis MMP-2 gene was positively correlated with the WT-1 gene, followed by CPA3, IGFBP2, FGFRL1, genes (PCC <0.65). Furthermore, a lower methylation level of MMP-2 gene was observed in AML compared to normal cases, which were negatively associated with MMP-2 gene expression. Gene enrichment analysis revealed MMP-2 gene and its positively associated gene were involved in biological processes such as angiogenesis, blood vessel maturation, and leukocyte transendothelial migration pathway. Notably, the MMP-2 mRNA expression was negatively linked with cell cycle and proliferation while positively associated with differentiation invasion and metastasis in AML. Conclusions In this study, we found that MMP-2 plays a significant role in AML progression and may serve as a potential prognostic biomarker and therapeutic target for the effective management of AML.