Abstract
BackgroundUveal melanoma (UVM) is the leading cause of eye-related mortality worldwide. This study aimed to explore the expression and prognostic value of matrix metalloproteinases (MMPs) in UVM.MethodsGene expression levels were obtained from the Gene Expression Omnibus (GEO) and Oncomine databases. Functional and pathway enrichment analyses were performed using the Metascape database. GeneMANIA was then applied to construct a protein-protein interaction network and identify the hub genes. Moreover, overall survival (OS) and disease-free survival (DFS) analysis for the hub genes was performed using the UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) online tool. Furthermore, TRRUST was used to predict the targets of the MMPs.ResultsOur results revealed that the transcriptional levels of MMP1, MMP9, MMP10, MMP11, MMP13, MMP14, and MMP17 were upregulated in UVM tissues compared to normal tissues. A protein-protein interaction (PPI) network was constructed and the top 50 hub genes were identified. The functions of MMPs and their neighboring proteins are mainly associated with ECM-receptor interaction, proteoglycans in cancer, the IL-17 signaling pathway, and microRNAs in cancer. Among the MMPs, MMP1/2/9/11/14/15/16/17/24 played significant roles in the progression of UVM from stage 3 to stage 4. We also found that the expression of MMP1, MMP2, MMP9, and MMP16 positively correlated with OS and DFS in patients with UVM. Additionally, 18 transcription factors associated with nine MMPs were identified.ConclusionsThe results of this study may provide potential biomarkers and targets for UVM. However, further studies are required to confirm these results.
Highlights
Uveal melanoma (UVM) is the leading cause of eye-related mortality worldwide
Matrix metalloproteinases (MMP) transcriptional differences in melanoma cancers and normal tissues We used the ONCOMINE database to explore the expression levels of MMPs in UVM and normal tissues (Fig. 1). This analysis revealed that the transcriptional levels of MMP1, MMP9, MMP10, MMP11, MMP13, MMP14, and MMP17 were upregulated in patients with UVM, while the transcriptional levels of MMP2, MMP7, and MMP24 were lower than those in normal samples
We discuss the relationship between UVM and MMP1, MMP2, MMP9, MMP11, MMP14, MMP15, MMP16, MMP17, and MMP24
Summary
Uveal melanoma (UVM) is the leading cause of eye-related mortality worldwide. This study aimed to explore the expression and prognostic value of matrix metalloproteinases (MMPs) in UVM. Uveal melanoma (UVM) is the most common primary malignant tumor of the eye in adults [1]. MMPs are considered as the main proteolytic enzymes in this process and the relation between MMPs and extracellular matrix components is interactive. According to their substrates, MMPs can be divided into six categories: (1) collagenases, including MMP1 (collagenase-1), MMP8 (collagenase-2), MMP13 (collagenase-3) with the main function of degrading collagen I, II, and III; (2) gelatinases, including MMP2 (gelatinase A) and MMP9 (gelatinase B), with the function of degrading collagen I and IV; (3) stromelysins, including MMP3 (stromelysin-1) and MMP11 (stromelysin-3); (4) MMP7. MMP activity is regulated at three levels: gene transcription, the activation of enzyme precursors and the effect of tissue inhibitors of metalloproteinases (TIMP)
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