Function Of Matrix Metalloproteinases Research Articles

The Role of Selected Matrix Metalloproteinases in the Pathogenesis of Gliomas

Abstract The progression of tumor formation is a multifactorial process that involves changes at different levels. Within this intricate molecular and cellular landscape of tumorigenesis, specific enzymes, namely matrix metalloproteinases (MMPs), emerge as pivotal contributors. They may influence this process at the level of tissue remodelling, angiogenesis, changes in cell signalling, invasion and metastasis, but may also serve as prognostic markers or therapeutic targets. Although the function of MMPs has been known for a long time, their specific role in the pathogenesis of brain tumors has only begun to be investigated in the last three decades. Deregulation of MMPs expression, frequently observed in brain tumor tissue, is associated with malignant phenotype, dependent on the grade of malignancy and associated with a worse prognosis. They participate in tissue remodelling under physiological and pathological conditions, which predetermines their action especially in the process of invasion and migration of tumor cells into the surrounding tissue. Related to their potential in tumor progression, they are also being investigated as possible targets in anticancer therapy. It would be very difficult to characterize in detail the role of all known MMPs in the context of brain tumor pathogenesis, so we have selected those that have an essential effect in this issue.

The multifaceted roles of matrix metalloproteinases in lung cancer.

Though the matrix metalloproteinases (MMPs) are widely investigated in lung cancer (LC), however, almost no review systematically clarify their multi-faced roles in LC. We investigated the expression of MMPs and their effects on survival of patients with LC, the resistance mechanisms of MMPs in anti-tumor therapy, the regulatory networks of MMPs involved, the function of MMPs inducing CSCLs, MMPs-related tumor immunity, and effects of MMP polymorphisms on risk of LC. High expression of MMPs was mainly related to poor survival, high clinical stages and cancer metastasis. Role of MMPs in LC are multi-faced. MMPs are involved in drug resistance, induced CSCLs, participated in tumor immunity. Besides, MMPs polymorphisms may increase risk of LC. MMPs might be promising targets to restore the anti-tumor immune response and enhance the killing function of nature immune cells in LC.

Matrix Metalloproteinase-Responsive Drug Delivery Systems.

Matrix metalloproteinases (MMPs) are a class of endopeptidases that are dependent on zinc and facilitate the degradation of extracellular matrix (ECM) proteins, thereby playing pivotal parts in human physiology and pathology. MMPs regulate normal tissue and cellular functions, including tissue development, remodeling, angiogenesis, bone formation, and wound healing. Several diseases, including cancer, inflammation, cardiovascular diseases, and nervous system disorders, have been linked to dysregulated expression of specific MMP subtypes, which can promote tumor progression, metastasis, and inflammation. Various MMP-responsive drug delivery and release systems have been developed by harnessing cleavage activities and overexpression of MMPs in affected regions. Herein, we review the structure, substrates, and physiological and pathological functions of various MMPs and highlight the strategies for designing MMP-responsive nanoparticles to improve the targeting efficiency, penetration, and protection of therapeutic payloads.

Matrix Metalloproteinases in Oral Health—Special Attention on MMP-8

Matrix metalloproteinases (MMPs) are a large family of Ca2+ and Zn2+ dependent proteolytic enzymes, able to cleave the various components of the extracellular matrix (ECM), as well as a range of other regulatory molecules. Several reports have proven the important role of both MMPs and their endogenous inhibitors, TIPMs, in oral health, the initial development of the tooth, and during enamel maturation. In this mini-review, we aim to summarize the literature information about the functions of MMPs, paying more attention to MMP-8 (collagenase-2 or neutrophil collagenase) in the development and progression of periodontitis, peri-implantitis, and carious lesions. We also emphasize the role of particular gene variants in MMP8 as predisposing factors for some oral diseases.

Matrix metalloproteinases: expression and regulation in the endometrium during the estrous cycle and at the maternal-conceptus interface during pregnancy in pigs.

Matrix metalloproteinases (MMPs) are a family of endoproteases produced by various tissues and cells and play important roles in angiogenesis, tissue repair, immune response, and endometrial remodeling. However, the expression and function of MMPs in the pig endometrium during the estrous cycle and pregnancy have not been fully elucidated. Thus, we determined the expression, localization, and regulation of MMP2, MMP8, MMP9, MMP12, and MMP13 in the endometrium throughout the estrous cycle and at the maternal-conceptus interface during pregnancy in pigs. Endometrial tissues during the estrous cycle and pregnancy and conceptus and chorioallantoic tissues during pregnancy were obtained and the expression of MMPs was analyzed. The effects of steroid hormones and cytokines on the expression of MMPs were determined in endometrial explant cultures. Expression levels of MMP12 and MMP13 changed during the estrous cycle, while expression of MMP2, MMP9, MMP12, and MMP13 changed during pregnancy. Expression of MMP2, MMP8, and MMP13 mRNAs was cell type-specific at the maternal-conceptus interface. Gelatin zymography showed that enzymatically active MMP2 was present in endometrial tissues. In endometrial explant cultures, estradiol-17β induced the expression of MMP8 and MMP12, progesterone decreased the expression of MMP12, interleukin-1β increased the expression of MMP2, MMP8, MMP9, and MMP13, and interferon-γ increased the expression of MMP2. These results suggest that MMPs expressed in response to steroids and cytokines play an important role in the establishment and maintenance of pregnancy by regulating endometrial remodeling and processing bioactive molecules in pigs.

Utilizing genetic code expansion to modify N-TIMP2 specificity towards MMP-2, MMP-9, and MMP-14

Matrix metalloproteinases (MMPs) regulate the degradation of extracellular matrix (ECM) components in biological processes. MMP activity is controlled by natural tissue inhibitors of metalloproteinases (TIMPs) that non-selectively inhibit the function of multiple MMPs via interaction with the MMPs' Zn2+-containing catalytic pocket. Recent studies suggest that TIMPs engineered to confer MMP specificity could be exploited for therapeutic purposes, but obtaining specific TIMP-2 inhibitors has proved to be challenging. Here, in an effort to improve MMP specificity, we incorporated the metal-binding non-canonical amino acids (NCAAs), 3,4-dihydroxyphenylalanine (L-DOPA) and (8-hydroxyquinolin-3-yl)alanine (HqAla), into the MMP-inhibitory N-terminal domain of TIMP2 (N-TIMP2) at selected positions that interact with the catalytic Zn2+ ion (S2, S69, A70, L100) or with a structural Ca2+ ion (Y36). Evaluation of the inhibitory potency of the NCAA-containing variants towards MMP-2, MMP-9 and MMP-14 in vitro revealed that most showed a significant loss of inhibitory activity towards MMP-14, but not towards MMP-2 and MMP-9, resulting in increased specificity towards the latter proteases. Substitutions at S69 conferred the best improvement in selectivity for both L-DOPA and HqAla variants. Molecular modeling provided an indication of how MMP-2 and MMP-9 are better able to accommodate the bulky NCAA substituents at the intermolecular interface with N-TIMP2. The models also showed that, rather than coordinating to Zn2+, the NCAA side chains formed stabilizing polar interactions at the intermolecular interface with MMP-2 and MMP-9. Our findings illustrate how incorporation of NCAAs can be used to probe—and possibly exploit—differential tolerance for substitution within closely related protein–protein complexes as a means to improve specificity.

Matrix metalloproteinases in oral cancer: A catabolic activity on extracellular matrix components

Zinc-dependent proteolytic enzymes known as matrix metalloproteinases (MMPs) are a class of structurally related enzymes that are known to be crucial in the catabolic turnover of extracellular matrix (ECM) components. MMPs are thought to control the activity of a number of non-ECM bioactive substrates, such as growth factors, cytokines, chemokines, and cell receptors, which control the tissue microenvironment. The interaction between cells and ECM plays a key role in normal development and differentiation of organism and many pathological states as well. The primary class of controlling proteases in the ECM is known as MMPs. Aspects of normal physiology and pathology depend on the ability of MMPs to change the structural integrity of tissues. Uncontrolled ECM turnover, tissue remodeling, inflammatory response, cell proliferation, and migration are pathogenic alterations that can result from an imbalance between the concentration of active metalloproteinases and their inhibitors (tissue inhibitors of metalloproteinases [TIMPs]). This detailed review provides some information on the function of MMPs in inflammatory, caries and periapical, cancer, and other oral diseases. Blood and saliva are the two biological fluids that are most frequently used to diagnose oral disorders. Most of the ECM components in patients undergo digestion to lower molecular weight forms, resulting in much higher amounts of MMPs in their saliva/blood than in healthy individuals. Conventional treatment successfully reduces the levels of MMPs which inhibits the progressive breakdown of collagens in ECM components.

Proteolytic cleavage of membrane proteins by membrane type-1 MMP regulates cancer malignant progression.

Strategies to develop cancer therapies using inhibitors that target matrix metalloproteinases (MMPs), particularly membrane type-1 MMP (MT1-MMP), have failed. This is predominantly attributed to the specificity of MMP inhibitors and numerous functions of MMPs; therefore, targeting substrates with such broad specificity can lead to off-target effects. Thus, new drug development for cancer therapeutics should focus on the ability of MT1-MMP to break down substrates, such as functional cell membrane proteins, to regulate the functions of these proteins that promote tumor malignancy. In this review, we discuss the mechanism by which proteolysis of cell surface proteins by MT1-MMP promotes progression of malignant tumor cells. In addition, we discuss the two protein fragments generated by limited cleavage of erythropoietin-producing hepatoma receptor tyrosine kinase A2 (EphA2-NF, -CF), which represent a promising basis for developing new cancer therapies and diagnostic techniques.

Utility of Matrix Metalloproteinases in the Diagnosis, Monitoring and Prognosis of Ovarian Cancer Patients.

Ovarian cancer is one of the most common gynecologic malignancies. It is characterized by a high mortality rate, which is mainly due to the asymptomatic course of the disease. In light of the high mortality rate and increasing morbidity, new diagnostic methods are being explored to enable earlier detection, better monitoring, and improved prognosis. Such diagnostic methods include the assessment of tumor markers in various biological samples. Among the markers currently being investigated, extracellular matrix metalloproteinases (MMPs) are of particular interest. The objective of this article was to compile the existing knowledge of MMPs in ovarian cancer patients and to describe their potential diagnostic utility. Additionally, this article provides an overview of the symptoms, complications, and risk factors associated with ovarian cancer and the role of MMPs in physiology and pathology. Preliminary results indicate that tissue expression and blood and body fluid levels of MMPs may be different in ovarian cancer patients than in healthy women. The expression and concentration of individual MMPs have been shown to be correlated with cancer stage and disease severity. In addition, the preliminary value of some of these enzymes in predicting prognosis is discussed. However, as the amount of data is limited, more studies are needed to fully evaluate the potential function of individual MMPs in ovarian cancer patients. Based on the knowledge gathered for this article, it seems that MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-13, are tentatively the most useful. A thorough evaluation of their utility as modern biomarkers in ovarian cancer requires further investigation.

Skin type specific photobiological response to visible light is mediated by constitutional melanin.

Visible light (VL) induces varying photobiological responses between skin types, likely influenced by inherent melanization. Individual typology angle (ITA) objectively measures skin types. We hypothesize that epidermal melanin content and distribution determine VL response. This study describes clinical and histologic responses to VL and examines the potential role of melanin in the underlying mechanistic pathways. We grouped enrolled participants by ITA (Light=5, Intermediate=4, Dark=7) per colorimetry (CR-400, Konica Minolta). Photoprotected sites were exposed daily to 480 J/cm2 of VL (Fiber-Lite High Intensity Illuminator, Series 180, Dolan Jenner Industries Inc.) for 4 days (total=1920 J/cm2 ), as tolerated. Treated and control sites were biopsied 96h after first exposure. We used hematoxylin and eosin and Fontana-Mason to assess histological changes and melanin deposition, respectively. p53 and Ki67 immunohistochemical stains were done to assess DNA damage and proliferation. Matrix metalloproteinase (MMP)-1 expression was detected by immunohistochemical staining and immunofluorescence microscopy. Darker skin did not tolerate the full VL regimen with blistering occurring in most subjects at doses of 220-880 J/cm2 . Intermediate and Dark skin showed tanning. Light skin developed erythema. p53 counts were highest in Intermediate, followed by Light skin, although this was not statistically significant. VL treatment led to MMP-1 expression and nuclear localization in keratinocytes in Dark and Intermediate but not in Light skin, however differences between groups were not statistically significant. Skin types demonstrate unique biological responses to VL. The role of melanin in photoprotection is well-defined. However, given the pro-apoptotic function of nuclear MMPs, we suggest a potential mechanism by which melanin may mediate VL-induced phototoxicity.

Role of matrix metalloproteinases in diabetic foot ulcers: Potential therapeutic targets

Diabetic foot ulcers (DFUs) are pathological states of tissue destruction of the foot or lower extremity in diabetic patients and are one of the serious chronic complications of diabetes mellitus. Matrix metalloproteinases (MMPs) serve crucial roles in both pathogenesis and wound healing. The primary functions of MMPs are degradation, which involves removing the disrupted extracellular matrix (ECM) during the inflammatory phase, facilitating angiogenesis and cell migration during the proliferation phase, and contracting and rebuilding the tissue during the remodeling phase. Overexpression of MMPs is a feature of DFUs. The upregulated MMPs in DFUs can cause excessive tissue degradation and impaired wound healing. Regulation of MMP levels in wounds could promote wound healing in DFUs. In this review, we talk about the roles of MMPs in DFUs and list potential methods to prevent MMPs from behaving in a manner detrimental to wound healing in DFUs.

Presumed Roles of APRO Family Proteins in Cancer Invasiveness.

Simple SummaryHere, we discuss the invasiveness of cancer cells in relation to APRO family proteins on the basis of understanding the function of matrix metalloproteinases (MMPs) and/or exosomes. Although APRO family proteins could regulate cancer invasiveness, alternative consequences might occur due to the distinctive effects of MMPs and/or exosomes containing certain microRNAs. Such knowledge could be of use to bring about novel strategies for cancer therapy.The APRO family members may be involved in the regulation of cell growth, migration, and/or invasion. Although an APRO protein could suppress the invasiveness of several cancer cells, it has been reported that overexpression of the same APRO protein could also promote the invasiveness and/or metastasis of the same cancer cells. In general, the invasiveness of cancer cells might be associated with the function of matrix metalloproteinases (MMPs) as well as with the function of certain exosomes. However, it has been shown that exosomes involving particular APRO proteins, MMPs, and/or microRNA could contribute to the regulation of invasiveness. Here, we discuss contradictory reports on invasiveness in relation to APRO family proteins on the basis of understanding the function of MMPs and/or various exosomes. A better understanding of those mechanisms could be of use to bring about innovative strategies for cancer treatment.

Fenretinide combines perturbation of signaling kinases, cell-extracellular matrix interactions and matrix metalloproteinase activation to inhibit invasion in oral squamous cell carcinoma cells.

Basement membrane invasion defines malignant transformation of surface premalignancy. Treatment of oral squamous cell carcinoma (OSCC) cells with the synthetic vitamin A derivative, fenretinide (4HPR), induces numerous cancer-preventive effects including suppression of basement membrane invasion, elimination of anchorage-independent growth, disruption of actin cytoskeletal components and inhibition of the invasion-enabling focal adhesive kinase. The purpose of this study was to elucidate 4HPR’s effects on additional invasion-relevant mechanisms including matrix metalloproteinase (MMP) activation and function, cell–extracellular matrix (ECM) attachments and interaction with a kinase that is essential for the epithelial–myoepithelial transformation i.e. c-Jun NH2-terminal kinase (JNK). Our data revealed that 4HPR binds with high affinity to the ATP-binding site of all three JNK isoforms with concurrent suppression of kinase function. Additional studies showed 4HPR treatment inhibited both OSCC cell–ECM adhesion and MMP activation and function. JNK downregulation and induced expression studies confirmed that the JNK3 isoform conveyed that largest impact on OSCC migration and invasion. Biodegradable polymeric implants formulated to preserve 4HPR’s function and bioavailability were employed to assess 4HPR’s chemopreventive impact on an OSCC tumor induction model. These studies revealed 4HPR local delivery significantly inhibited OSCC tumor size, mitotic indices and expression of the endothelial marker, erythroblast transformation-specific-related gene with concurrent increases in tumor apoptosis (cleaved caspase-3). Collectively, these data show that 4HPR suppresses invasion at multiple sites including ‘outside-in’ signaling, cell–ECM interactions and suppression of MMPs. These functions are also essential for physiologic function. Regulation is therefore essential and reinforces the pharmacologic advantage of local delivery chemopreventive formulations. .

Dentin Matrix Metalloproteinases: A Futuristic Approach Toward Dentin Repair and Regeneration.

Matrix metalloproteinases (MMPs) have been linked to modulating healing during the production of tertiary dentin, as well as the liberation of physiologically active molecules and the control of developmental processes. Although efforts to protect dentin have mostly centered on preventing these proteases from doing their jobs, their role is actually much more intricate and crucial for dentin healing than anticipated. The role of MMPs as bioactive dentin matrix components involved in dentin production, repair, and regeneration is examined in the current review. The mechanical characteristics of dentin, especially those of reparative and reactionary dentin, and the established functions of MMPs in dentin production are given particular attention. Because they are essential parts of the dentin matrix, MMPs should be regarded as leading applicants for dentin regeneration.

Evaluation of the matrix metalloproteinase 9 (MMP9) inhibitor Andecaliximab as an Anti-invasive therapeutic in Head and neck squamous cell carcinoma

ObjectivesLocoregional and lymphovascular involvement of invasive head and neck squamous cell carcinoma (HNSCC) complicates curative treatment. Matrix metalloproteinase (MMP) 9 is a negative prognostic marker in HNSCC and targets multiple extracellular matrix (ECM) substrates, where it contributes to breaching basement membrane and stromal barriers enabling invasive spread. Andecaliximab (ADX) is a second-generation MMP9 inhibitor well tolerated in clinical trials of gastric and pancreatic adenocarcinoma. The impact of selective MMP9 targeting by ADX in HNSCC has not been evaluated. Materials and MethodsEstablished and patient-derived xenograft (PDX) cell lines were utilized in HNSCC invasion assays to determine the inhibitory ability of MMP9-mediated invasion by ADX. MMP9 expression was confirmed using immunohistochemistry (IHC) and immunoblotting. ECM degradation was evaluated with confocal microscopy. Cell invasion from tumor spheroids was monitored by phase microscopy. Histological evaluation was used to determine ADX efficacy in three-dimensional organotypic cultures containing cancer associated fibroblasts (CAFs). ResultsMMP9 was expressed in all established and PDX-derived cell lines. While the broad spectrum clinical MMP inhibitor marimastat (BB2516) blocked HNSCC invadopodia function and tumor spheroid invasion, ADX treatment failed to inhibit invadopodia-based matrix degradation, tumor cell or fibroblast-driven ECM invasion in collagen I-based matrices. ConclusionADX monotherapy was ineffective at blocking initial MMP-dependent events of HNSCC invasion, likely due to redundant functions of additional non-targeted MMPs produced by tumor cells and microenvironment. Combination of ADX with existing and emerging therapies targeting additional MMP activation pathways may warrant future investigation.

Matrix Metalloproteinases and Their Inhibitors in Pulmonary Fibrosis: EMMPRIN/CD147 Comes into Play.

Pulmonary fibrosis (PF) is characterized by aberrant extracellular matrix (ECM) deposition, activation of fibroblasts to myofibroblasts and parenchymal disorganization, which have an impact on the biomechanical traits of the lung. In this context, the balance between matrix metalloproteinases (MMPs) and their tissue inhibitors of metalloproteinases (TIMPs) is lost. Interestingly, several MMPs are overexpressed during PF and exhibit a clear profibrotic role (MMP-2, -3, -8, -11, -12 and -28), but a few are antifibrotic (MMP-19), have both profibrotic and antifibrotic capacity (MMP7), or execute an unclear (MMP-1, -9, -10, -13, -14) or unknown function. TIMPs are also overexpressed in PF; hence, the modulation and function of MMPs and TIMP are more complex than expected. EMMPRIN/CD147 (also known as basigin) is a transmembrane glycoprotein from the immunoglobulin superfamily (IgSF) that was first described to induce MMP activity in fibroblasts. It also interacts with other molecules to execute non-related MMP aactions well-described in cancer progression, migration, and invasion. Emerging evidence strongly suggests that CD147 plays a key role in PF not only by MMP induction but also by stimulating fibroblast myofibroblast transition. In this review, we study the structure and function of MMPs, TIMPs and CD147 in PF and their complex crosstalk between them.

Water molecule-mediated selective inhibition of bacterial zinc metalloproteinases by non-hydroxamate compounds: Ab initio molecular simulations

UDP-3-O-acyl-N acetylglucosamine deacetylase (LpxC), Zn metalloenzyme for Gram-negative bacteria is an attractive target for developing novel therapeutic agents. Since LpxC has the similar binding pocket as the human matrix metalloproteinases (MMPs), LpxC inhibitors might also inhibit MMP functions producing side effects in human bodies. Here, we investigated specific interactions between LpxC/MMP and their inhibitors using ab initio molecular simulations to elucidate the reason of selective inhibition for LpxC by non-hydroxamate compounds. The evaluated binding properties between LpxC and the compounds are comparable to the trend of their observed inhibitory affinities. It was also elucidated that compound 22 binds most strongly to LpxC due to its specific interactions with Zn ion and Asp241 side chain of LpxC. In contrast, the interactions between the compounds and MMP are significantly weakened due to the water molecules, which are tightly coordinated with the Zn ion in MMP and interrupt the binding of the compounds to the Zn ion. Accordingly, the present molecular simulations revealed that these water molecules around the Zn ion in MMP are causally related to the selective inhibition of these compounds for LpxC rather than MMP.

The dual roles of three MMPs and TIMP in innate immunity and metamorphosis in the silkworm, Bombyx mori.

The matrix metalloproteinases (MMPs) and their endogenous inhibitory factors, tissue inhibitors of metalloproteinases (TIMPs), are implicated in many diseases. However, the mammalian MMPs (> 20) and TIMPs (> 3) are larger in number, and so little is known about their individual roles in organisms. Hence, we have systematically studied the roles of all three MMPs and one TIMP in silkworm innate immunity and metamorphosis. We observed that MMPs and TIMP are highly expressed during the pupation stage of the silkworms, and TIMP could interact with each MMPs. High-activity MMPs and low-activity TIMP may enhance the infection of B. mori nucleopolyhedrovirus in both in vitro and in vivo. MMPs' knockout and TIMP overexpression delayed silkworm development and even caused death. Interestingly, different MMPs' knockout led to different tubular tissue dysplasia. These findings provide insights into the conserved functions of MMPs and TIMP in human organogenesis and immunoregulation.

Matrix metalloproteinases and their inhibitors - pleiotropic functions in insect immunity and metamorphosis.

Matrix metalloproteinases (MMPs) enable tissue remodeling and immune responses by degrading extracellular matrix proteins. They are regulated by tissue inhibitors of metalloproteinases (TIMPs). Mammals produce more than 20 MMPs but insects produce fewer than 3, at odds with the extensive tissue remodeling required during metamorphosis and inflammation. Addressing this apparent paradox, Liu etal. demonstrate the pleiotropic functions of silkworm MMPs and TIMP. They measured expression levels during pupation and during a response to viral infection in transgenic overexpression and knockout lines for selected MMP/TIMP genes. This confirmed the multiple roles of these key enzymes in insect immunity and metamorphosis. Comment on https://doi.org/10.1111/febs.16313.

MMP1 and MMP9 are potential prognostic biomarkers and targets for uveal melanoma

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.