Development Of Uveal Melanoma Research Articles

Iris melanoma in an Australian cohort.

To report the clinicopathological features and epidemiology of iris melanoma in Queensland, Australia. This was a retrospective study of 86 patients with iris melanoma treated between 2001 and 2022 at the Queensland Ocular Oncology Service, Brisbane, Australia. Main outcome measures included demographics, clinical and phenotypic features, age-adjusted incidence and relative survival. Eighty-six patients (63% female) were included. Mean age was 54 years (range 17-82 years). The majority of patients (97%) were Caucasian, with blue eyes, fair skin and Fitzpatrick Skin Type I or II. Demographic features and clinical history showed a tendency for high ultraviolet radiation (UVR) exposure in the cohort. Histopathology was available in 69 cases (82%), and of these, 77% tumours were of spindle cell origin, with low-risk genetic profiles. Patients were followed for a mean of 8 years (median 7, range 1-21 years) after diagnosis, and only one case of metastasis was documented. The association of iris freckles, history of UVR exposure and dermatologic findings supports the role of UVR in iris melanoma. Occupation and avocation history, as well as evaluation of iris freckles may offer an easily accessible way of stratifying the risk of an individual for development of UVR-related uveal melanoma.

Prognostic significance of melanogenesis pathway and its association with the ultrastructural characterisation of melanosomes in uveal melanoma

BackgroundPigmentation could be a relevant prognostic factor in uveal melanoma (UM) development. Microphthalmia-associated transcription factor (MITF) regulates melanin synthesis by activating tyrosinase-related protein 2 (TYRP2) and silver protein (SILV) that...

Darovasertib, a novel treatment for metastatic uveal melanoma.

The FDA granted orphan drug designation to darovasertib, a first-in-class oral, small molecular inhibitor of protein kinase C (PKC), for the treatment of uveal melanoma, on 2 May 2022. Primary uveal melanoma has a high risk of progressing to metastatic uveal melanoma, with a poor prognosis. The activation of the PKC and mitogen-activated protein kinase pathways play an essential role in the pathogenesis of uveal melanoma, and mutations in the G protein subunit alpha q (GNAQ), and G protein subunit alpha11 (GNA11) genes are considered early events in the development of uveal melanoma. Compared to other PKC inhibitors, such as sotrastaurin and enzastaurin, darovasertib is significantly more potent in inhibiting conventional (α, β) and novel (δ, ϵ, η, θ) PKC proteins and has a better tolerability and safety profile. Current Phase I/II clinical trials indicated that darovasertib, combined with the Mitogen-activated protein kinase/Extracellular (MEK) inhibitors, binimetinib or crizotinib, produced a synergistic effect of uveal melanoma. In this article, we summarize the development of drugs for treating uveal melanomas and discuss problems associated with current treatments. We also discuss the mechanism of action, pharmacokinetic profile, adverse effects, and clinical trial for darovasertib, and future research directions for treating uveal melanoma.

Prognostic analysis of uveal melanoma based on the characteristic genes of M2-type macrophages in the tumor microenvironment

Uveal melanoma arises from stromal melanocytes and is the most prevalent primary intraocular tumor in adults. It poses a significant diagnostic and therapeutic challenge due to its high malignancy and early onset of metastases. In recent years, there has been a growing interest in the role of diverse immune cells in tumor cell development and metastasis. Using The Cancer Genome Atlas and the gene expression omnibus databases, and the CIBERSORT method, we investigated the topography of intra-tumor immune infiltration in uveal melanoma in this research. We evaluated the prognosis of uveal melanoma patients using the M2 macrophage immune cell infiltration score in conjunction with clinical tumor patient data. We built a prognostic model based on the distinctive genes of M2 macrophages and combined it with patients’ clinical data in the database; we ran a survival prognostic analysis to authenticate the model’s accuracy. The functional study revealed the importance of macrophage-associated genes in the development of uveal melanoma. Moreover, the reliability of our prediction model was verified by combining tumor mutational load, immune checkpoint, and drug sensitivity, respectively. Our study provides a reference for the follow-up study of uveal melanoma.

Association of BARD1 and BRIP1 Gene Polymorphisms with the Risk of Uveal Melanoma.

Considering the limited information about the role of hereditary predisposition to the development of uveal melanoma, we have performed an analysis of the frequencies of BARD1 (rs1048108, rs2229571, rs2070094) and BRIP1 (rs4986764) gene polymorphisms in patients with uveal melanoma and benign choroidal nevus in comparison with healthy volunteers (control). It has been found that the minor alleles of BRIP1 rs4986764 and BARD1 rs2070094 polymorphisms, as well as the homozygosity of T allele at the BARD1 rs1048108 locus are common genetic markers for the predisposition to uveal melanoma and benign choroidal nevus, while the homozygous genotype GG for the BARD1 rs2229571 polymorphism is a specific marker for the predisposition to uveal melanoma and progressive choroidal nevus. We have also found that the heterozygous genotype at BARD1 rs1048108 polymorphic locus is a specific marker for protection against uveal melanoma and progressive choroidal nevus. Thus, our results indicate the advisability of studying polymorphisms of the BARD1 gene (rs1048108, rs2229571, and rs2070094) and the BRIP1 gene (rs4986764) in patients with uveal melanoma and progressive choroidal nevus. The obtained findings can be used for forming risk groups, prevention of uveal melanoma, and differential diagnosis of intraocular neoplasms.

IMPACT OF HARMFUL ENVIRONMENTAL FACTORS ON THE VISUAL SYSTEM

Harmful effects of climate change on health include many pathologies. There are many ways that environmental factors affect the visual system, including exposure to UV rays on the cornea, lens, retina, and the development of cataracts, glaucoma, uveal melanoma, photokeratitis, and others. Cataract development is also caused by infrared radiation. In the case of both mentioned types of radiation, the development of oxidative stress or the disruption of the protective mechanism against it is thought to be a pathogenic mechanism. The visual system is also affected by dust, air pollution, active and passive smoking, changes in various climate parameters (including precipitation, temperature, humidity, albedo). In order to avoid problems, it is necessary to pay attention to the hygiene of the visual system, which includes the use of appropriate protective equipment, timely cleaning of contaminated eyes, care for dry eye syndrome, correct use of contact lenses and etc.. The release of carbon into the environment has long-term negative effects on the health of the population, mainly due to the increase in temperature and the problems caused by the latter. Single-use medical instruments and equipment contribute to the mass generation of clinical and non-clinical waste and release large amounts of carbon. Ophthalmosurgical manipulations (including cataract surgeries) are characterized by the highest quantitative index in the world. This makes cataract surgery an obvious target for reducing carbon emissions. Because of the above, it is important to put into practice the principle of "The 5 R" provided in modern medicine, which implies reduction, reuse, recycling, review and research. It is important to understand all of the above and take into account in everyday life both ordinary individuals and ophthalmologists and health care managers.

MicroRNA-592 serves as a novel tumor suppressor in Uveal melanoma: bioinformatics analysis and in vitro cell function verification

ABSTRACT Uveal melanoma (UVM), one common eye tumor in adults, is related with a high risk of metastasis and poor prognosis. Studies have shown that many miRNAs are abnormally expressed in UVM tissues, and play an important regulatory role in the cell proliferation, invasion, and metastasis of UVM. Therefore, it is of great significance to analyze the expression characteristics of microRNAs (miRNAs) in UVM and clarify the role of miRNA in the tumorigenesis and development of UVM. In this study, we firstly downloaded and analyzed miRNA expression data of UVM tissues in TCGA (The Cancer Genome Atlas) database to select the differential expressed miRNAs in different clinical stages (IIA, IIB, IIIA, IIIB, IV). Compared with other stages, microRNA-592 (miR-592) was up-regulated in stage IV UVM patients. Then we used several bioinformatics tools including miRbase, miRDB, RNA22 and TargetScan, and found that it was be conserved in different species. Cell viability was determined by Cell Counting Kit-8. The proliferation and invasion of MUM-2B and C819 cells was measured using Edu assay and Transwell assay. We found that silencing miR-592 enhanced the progression of UVM cells, while miR592 overexpression inhibited the cell growth and invasion. The target genes of miR-592 were predicted by three webservers (miRDB, RNA22, and TargetScan), and verified by Real-Time PCR (qPCR). This is the first study to explore the role of miR-592 in malignant progression of UVM by bioinformatics and cell experiments. Our study suggests that tumor suppressor miR-592 may function as potential therapeutic target and biomarker for UVM.

Identification of 5 microRNA biomarkers associated with the prognosis of uveal melanoma.

To uncover the role of microRNAs in the occurrence and development of uveal melanoma (UM), we used R language packages in this study to analyze the correlations between the expression of microRNA isoforms, their target genes, and the clinical data for UM patients retrieved from The Cancer Genome Atlas (TCGA). We used Weighted Correlation Network Analysis (WGCNA) to divide the expression profiles of different microRNAs into 10 modules, among which blue and yellow modules were associated with UM survival. Hsa-miR-513a-5p, miR-506-3p, miR-508-3p, miR-140-3p, and miR-103a-2-5p were further identified as the top 5 node microRNAs based on the risk scores in both modules using least absolute shrinkage and selection operator (LASSO) Cox regression analysis. After combining these 5 microRNAs into an integrated risk signature, the prognostic performance of the risk signature was evaluated by area under the receiver operating characteristic (AUROC) curve, and their association with UM clinical characteristics was further analyzed using multiple Cox regression. Our results showed that this risk signature was sensitivity and specificity, and could serve as an independent prognostic factor. In addition, Spearman correlation analysis showed that expression of almost all target mRNAs were significantly positively or negatively correlated with the associated microRNAs. The gene ontology (GO), pathways, and disease enrichment analyses also showed that these 5 microRNAs were closely related to the incidence and progression of tumor, indicating their potential for predicting the outcome of UM.

Uveal Melanoma

Uveal melanoma, a malignant proliferation of melanocytes in the uvea, is the most common primary tumor of the eye in adults. The purpose of this review is to discuss the risk factors, clinical presentation, diagnosis, prognosis, and management, while providing information about novel viewpoints and tools for diagnosis and treatment of uveal melanoma. Blue-light exposure, BAP1 polymorphisms, complete monosomy 3, and history of ocular melanocytosis are the greatest risk factors for the development of uveal melanoma. Uveal melanoma can first present either on routine eye exam or upon presentation with flashes, floaters, and visual field defects. Diagnosis of uveal melanoma is made with anterior segment ocular coherence tomography or ultrasound biomicroscopy. Fine-needle biopsy of the lesion often follows diagnosis, with gene expression profiling being the best prognostic indicator for uveal melanoma. The gold standard for treatment of uveal melanoma is plaque brachytherapy. Other treatment possibilities for uveal melanoma include enucleation, charged-particle radiation therapy, transpupillary thermotherapy and photodynamic thermotherapy. Uveal melanoma may be fatal if untreated and subsequently metastasizes. Hopefully, earlier detection methods including the use of circulating tumor cells, circulating tumor DNA, and circulating MicroRNA and subsequent treatment using novel targeted therapies like high-intensity focused ultrasound, iontophoresis and electrochemotherapy would be crucial to improving prognosis in the future.

The effect of sex hormones and pregnancy on development and progression of uveal melanoma

The analysis of literature revealed that men experience uveal melanoma (UM) more frequently and with worse prognosis. There are also descriptions of an aggressive course of UM in pregnant women. These facts prompted researchers to analyze the effect of sex hormones and pregnancy on the development and progression of UM. Many years of international experience have refuted the presence of a reliable difference between 5-year survival and 5-year survival without metastases between non-pregnant women with UM and pregnant women with UM. That data is regarded as level 3 evidence. The experts have concluded that UM is not a contraindication to current or future pregnancy, and exogenous hormones (oral contraceptives or hormone replacement therapy) do not affect the incidence and prognosis of UM. Publications provide evidence of expression of the receptors of certain sex hormones (ER, ERRα, LH and LHRH) in primary UM, as well as overexpression of the ESR1 and ESR2 genes in UM with poor predictive characteristics. Overall AR mRNA expression in UM was low, but it was higher in epithelial UMs. The fact of expression of estrogen receptors in UM gives grounds to experiment with them as a target for therapy.

PARK7/DJ-1 inhibition decreases invasion and proliferation of uveal melanoma cells.

PARK7/DJ-1 is an oncogene that is associated with tumorigenesis in many cancers. Recent studies have demonstrated the importance of DJ-1 in the origin and development of uveal melanoma (UM). We present an analysis of the role of the DJ-1 protein in UM cells, especially in its effect on proliferation and migration. UM cells from a primary tumor, Mel 270, and its liver metastasis, OMM2.5, were transfected with lentiviral-delivered shRNA against PARK7/DJ-1. Evaluation of cell migration and proliferation was performed using the xCELLigence real-time cell analyzer (RTCA). The effect of DJ-1 inhibition on the PTEN-Akt signaling pathway was also studied by immunoblotting. The silencing of PARK7/DJ-1 oncoprotein expression produced a significant decrease of phosphorylated Akt (S473) in Mel270 and in metastatic OMM2.5 UM cells with no alteration on tumor suppressor PTEN expression. The diminution of PARK7/DJ-1 expression significantly inhibited real-time proliferation and invasion of Mel270 and OMM2.5 and the invasion potential of the metastatic cells. DJ-1 appears to play a key role on the PTEN/Akt pathway in UM. DJ-1 inhibition appears to have a negative effect on proliferation and invasion of UM cells. This suggests DJ-1 as a potential therapeutic target in UM.

Validation of the Relationship Between Iris Color and Uveal Melanoma Using Artificial Intelligence With Multiple Paths in a Large Chinese Population.

Previous studies have shown that light iris color is a predisposing factor for the development of uveal melanoma (UM) in a population of Caucasian ancestry. However, in all these studies, a remarkably low percentage of patients have brown eyes, so we applied deep learning methods to investigate the correlation between iris color and the prevalence of UM in the Chinese population. All anterior segment photos were automatically segmented with U-NET, and only the iris regions were retained. Then the iris was analyzed with machine learning methods (random forests and convolutional neural networks) to obtain the corresponding iris color spectra (classification probability). We obtained satisfactory segmentation results with high consistency with those from experts. The iris color spectrum is consistent with the raters’ view, but there is no significant correlation with UM incidence.

Retraction.

Retraction: "Ras-PI3K-AKT signaling promotes the occurrence and development of uveal melanoma by downregulating H3K56ac expression," by Yaping Li, Dajun Sun, Weixuan Sun, Dexin Yin, J Cell Physiol. 2019; 16032-16042: The above article, published online on 15 February 2019 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/full/10.1002/jcp.28261), has been retracted by agreement between the journal's Editor in Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. Several flaws and inconsistencies between results presented and experimental methods described were found, the editors consider the conclusions of this article to be invalid. The authors collaborated in the investigation initially, but were not available for a final confirmation of the retraction.

Sunlamp use is a risk factor for uveal melanoma: a meta-analysis

ObjectiveAdvancements in the treatment of uveal melanoma have not improved survival; therefore, identifying modifiable risk factors is critical to improving outcomes. This study aims to investigate the association between sunlamp use and the development of uveal melanoma. DesignThis study is designed as a meta-analysis. MethodsLiterature was searched and reviewed through the MEDLINE (with both OVID and PubMed), EMBASE, MD Consult, and Web of Science databases. These databases were searched from 1966 to 2019 using the following keywords to identify articles examining risk factors for uveal melanoma: ultraviolet, sun, sunlight, uveal melanoma, eye cancer, eye melanoma, nevus, and risk factor. All articles were evaluated for inclusion based on methodology and data reporting association between sunlamp use and uveal melanoma. The Meta-analysis of Observational Studies in Epidemiology guidelines and the Newcastle-Ottawa Scale were used to assess data quality and validity. A random effects model was employed. ResultsA total of 5 studies, enrolling a total of 1753 uveal melanoma cases and 3399 controls were included in this meta-analysis. The results of this study showed a positive association between sunlamp use and uveal melanoma (odds ratio = 2.15; 95% confidence interval 1.27–3.64). Meta-regression of between study heterogeneity did not reveal a statistically significant association when publication year, site latitude, melanoma tissue location (specifically, inclusion of iris tumors), or control type (population versus clinic) were evaluated. ConclusionThis meta-analysis identified a statistically significant association between sunlamp use and uveal melanoma, supporting sunlamp use as a modifiable risk factor for uveal melanoma.

The Impact of Ultraviolet Radiation on the Aetiology and Development of Uveal Melanoma.

Simple SummaryUveal melanoma (UM) is the most common form of eye cancer in adults. It has a poor prognosis and limited treatment options. UM, unlike cutaneous melanoma (CM), historically lacks convincing evidence of causative ultraviolet radiation (UVR) involvement in its pathophysiology and ex vivo experimentation has suggested that UVR cannot even penetrate through the anterior ocular structures to initiate carcinogenic changes. Opposing this idea are the recent publications of UVR damage signatures in UM samples, even in those arising from the posterior uvea. This review provides an up-to-date exploration of endogenous and exogenous factors that can impact ocular susceptibility UVR, whether they form any relationship with UM risk or incidence.Uveal melanoma (UM) is currently classified by the World Health Organisation as a melanoma caused by risk factors other than cumulative solar damage. However, factors relating to ultraviolet radiation (UVR) susceptibility such as light-coloured skin and eyes, propensity to burn, and proximity to the equator, frequently correlate with higher risk of UM. These risk factors echo those of the far more common cutaneous melanoma (CM), which is widely accepted to be caused by excessive UVR exposure, suggesting a role of UVR in the development and progression of a proportion of UM. Indeed, this could mean that countries, such as Australia, with high UVR exposure and the highest incidences of CM would represent a similarly high incidence of UM if UVR exposure is truly involved. Most cases of UM lack the typical genetic mutations that are related to UVR damage, although recent evidence in a small minority of cases has shown otherwise. This review therefore reassesses statistical, environmental, anatomical, and physiological evidence for and against the role of UVR in the aetiology of UM.

Association of TYRP1 with hypoxia and its correlation with patient outcome in uveal melanoma.

Molecular mechanisms of uveal melanoma development in association with high pigmentation are unclear. Tyrosinase Related Protein (TYRP1) is not only one of the important melanogenesis marker that contributes to melanin synthesis, but can also prevents the melanocyte death. The induction of melanogenesis leads to induction of HIF-1α which can affect the behavior of melanoma cells and its surrounding environment. The aim of our study was to determine the expression of TYRP1 and HIF-1α at the protein and RNA level and determine its prognostic significance. In the present study, the expression of TYRP1 and HIF-1α was investigated on 61 formalin-fixed paraffin-embedded choroidal melanoma samples by immunohistochemistry. Fresh 50 samples were validated by real-time PCR. Results were correlated with clinicopathological parameters and Kaplan-Meier was performed to determine the prognostic significance. High immunoexpression of TYRP1 and HIF-1α was present in 61 and 54% of patients, respectively. Both TYRP1 and HIF-1α correlated well with high pigmentation and BAP1 (BRCA1 Associated Protein-1) loss (p < 0.05) at IHC level as well as transcriptional level. There was reduced metastatic free survival in patients with necrosis and this was statistically significant (p = 0.010). Our findings indicate that TYRP1 can be used as a potential biomarker in the development of targeted therapy in UM. Further studies on melanogenesis markers associated with TYRP1 could provide us a better understanding in this field.

Involvement of mutant and wild-type CYSLTR2 in the development and progression of uveal nevi and melanoma

BackgroundActivating Gαq signalling mutations are considered an early event in the development of uveal melanoma. Whereas most tumours harbour a mutation in GNAQ or GNA11, CYSLTR2 (encoding G-protein coupled receptor CysLT2R) forms a rare alternative. The role of wild-type CysLT2R in uveal melanoma remains unknown.MethodsWe performed a digital PCR-based molecular analysis of benign choroidal nevi and primary uveal melanomas. Publicly available bulk and single cell sequencing data were mined to further study mutant and wild-type CYSLTR2 in primary and metastatic uveal melanoma.Results1/16 nevi and 2/120 melanomas carried the CYSLTR2 mutation. The mutation was found in a subpopulation of the nevus, while being clonal in both melanomas. In the melanomas, secondary, subclonal CYSLTR2 alterations shifted the allelic balance towards the mutant. The resulting genetic heterogeneity was confirmed in distinct areas of both tumours. At the RNA level, further silencing of wild-type and preferential expression of mutant CYSLTR2 was identified, which was also observed in two CYSLTR2 mutant primary melanomas and one metastatic lesion from other cohorts. In CYSLTR2 wild-type melanomas, high expression of CYSLTR2 correlated to tumour inflammation, but expression originated from melanoma cells specifically.ConclusionsOur findings suggest that CYSLTR2 is involved in both early and late development of uveal melanoma. Whereas the CYSLTR2 p.L129Q mutation is likely to be the initiating oncogenic event, various mechanisms further increase the mutant allele abundance during tumour progression. This makes mutant CysLT2R an attractive therapeutic target in uveal melanoma.

Circ_0119872 promotes uveal melanoma development by regulating the miR-622/G3BP1 axis and downstream signalling pathways

BackgroundThe abnormal expression of circular RNAs (circRNAs) in uveal melanoma (UM) has been revealed, but the specific underlying molecular mechanism of their association with UM development has not been fully explored.MethodsThe levels of circ_0119872, G3BP1 and miR-622 in UM cell lines and tissues were determined by quantitative real-time PCR (qRT-PCR) and western blotting assays. In vitro and in vivo assays were performed to investigate the function of circ_0119872 in the tumorigenesis of UM cells. The relationships among circ_0119872, miR-622 and G3BP1 were predicted using bioinformatic tools and verified by RNA-FISH, RNA pull-down and dual-luciferase reporter assays. The effects of circ_0119872 on Wnt/β-catenin and mTOR signalling pathways were determined by gene set enrichment analysis (GSEA) and western blotting.ResultsWe found that circ_0119872 is upregulated in UM cell lines and tissues. Moreover, overexpression of circ_0119872 promotes the malignancy of UM cells, while silencing of circ_0119872 inhibits it. In addition, circ_0119872 can directly interact with miR-622 as a miRNA sponge that regulates the expression of the miR-622 target gene G3BP1 as well as downstream Wnt/β-catenin and mTOR signalling pathways.ConclusionsCirc_0119872 may act as an oncogene in UM through a novel circ_0119872/miR-622/G3BP1 axis, activating the Wnt/β-catenin and mTOR signalling pathways, which in turn may provide potential biomarkers and therapeutic targets for the management of UM.

Retraction.

Retraction: "Ras-ERK1/2 signaling promotes the development of uveal melanoma by downregulating H3K14ac," by Yaping Li, Weixuan Sun, Dajun Sun, Dexin Yin, J Cell Physiol. 2019; 16011-16020: The above article, published online on February 15, 2019 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/full/10.1002/jcp.28259), has been been retracted by agreement between the journal's Editor-in-Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. Several flaws and inconsistencies between results presented and experimental methods described were found, the editors consider the conclusions of this article to be invalid. The authors collaborated in the investigation initially, but were not available for a final confirmation of the retraction.

Extracellular Protease ADAMTS1 Is Required at Early Stages of Human Uveal Melanoma Development by Inducing Stemness and Endothelial-Like Features on Tumor Cells.

Extracellular matrix remodeling within the tumor microenvironment has been recognized as a relevant dynamic framework during tumor growth. However, research on proteases that trigger this remodeling keeps revealing a wide range of actions including both pro- and anti-tumorigenic. The extracellular protease ADAMTS1 exemplifies this dual role. In this work, we first confirmed a positive correlation of ADAMTS1 with endothelial-like phenotype of human melanoma cells together with the finding of associated signatures, including key genes such as endothelial CDH5. Using a CRISPR-Cas9 approach, we observed that the inhibition of ADAMTS1 in an aggressive uveal melanoma model compromised its endothelial-like properties, and more importantly, caused a robust blockade on the progression of tumor xenografts. Although vasculature emerged affected in ADAMTS1-deficient tumors, the most relevant action implied the downregulation of endothelial CDH5 in tumor cells, in association with stemness markers. Indeed, melanoma sphere assays also revealed a deficient commitment to form spheres in the absence of ADAMTS1, directly correlating with stemness markers and, remarkably, also with CDH5. Finally, taking advantage of advanced bioinformatics tools and available public data of uveal melanomas, we disclosed new prognosis factors, including endothelial elements and ADAMTS proteases. Our findings support the key role of ADAMTS proteases for uveal melanoma development since earlier stages, modulating the complex crosstalk between extracellular matrix and the induction of stemness and endothelial-like features. To our knowledge, this is the first report that supports the development of therapeutic targets on the extracellular matrix to overcome uveal melanoma.