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A quantitative proteomic analysis of 53 metastasizing and 47 non-metastasizing primary uveal melanoma (pUM) was pursued for insights into UM metastasis and protein biomarkers. The metastatic status of the pUM specimens was defined based on clinical data, survival histories, prognostic analyses, and liver histopathology. LC MS\/MS iTRAQ technology, the Mascot search engine, and the UniProt human database were used to identify and quantify pUM proteins relative to the normal choroid excised from UM donor eyes. The determined proteomes of all 100 tumors were very similar, encompassing a total of 3935 pUM proteins. Proteins differentially expressed (DE) between metastasizing and non-metastasizing pUM (n = 402) were employed in bioinformatic analyses that predicted significant differences in the immune system between metastasizing and non-metastasizing pUM. The immune proteins (n = 778) identified in this study support the immune-suppressive nature and low abundance of immune checkpoint regulators in pUM, and suggest CDH1, HLA-DPA1, and several DE immune kinases and phosphatases as possible candidates for immune therapy checkpoint blockade. Prediction modeling identified 32 proteins capable of predicting metastasizing versus non-metastasizing pUM with 93% discriminatory accuracy, supporting the potential for protein-based prognostic methods for detecting UM metastasis.<\/jats:p>","DOI":"10.3390\/cancers13143520","type":"journal-article","created":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T10:13:42Z","timestamp":1626257622000},"page":"3520","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Proteomics of Primary Uveal Melanoma: Insights into Metastasis and Protein Biomarkers"],"prefix":"10.3390","volume":"13","author":[{"given":"Geeng-Fu","family":"Jang","sequence":"first","affiliation":[{"name":"Cole Eye Institute, Cleveland Clinic, Cleveland, OH 44195, USA"},{"name":"Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack S.","family":"Crabb","sequence":"additional","affiliation":[{"name":"Cole Eye Institute, Cleveland Clinic, Cleveland, OH 44195, USA"},{"name":"Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belinda","family":"Willard","sequence":"additional","affiliation":[{"name":"Proteomics and Metabolomics Facility, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Kalirai","sequence":"additional","affiliation":[{"name":"Liverpool Ocular Oncology Research Centre, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, William Henry Duncan Building, West Derby Street, Liverpool L7 8TX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun D.","family":"Singh","sequence":"additional","affiliation":[{"name":"Cole Eye Institute, Cleveland Clinic, Cleveland, OH 44195, USA"},{"name":"Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1464-2069","authenticated-orcid":false,"given":"Sarah E.","family":"Coupland","sequence":"additional","affiliation":[{"name":"Liverpool Ocular Oncology Research Centre, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, William Henry Duncan Building, West Derby Street, Liverpool L7 8TX, UK"},{"name":"Liverpool Clinical Laboratories, Liverpool University Hospitals NHS Foundation Trust, Duncan Building, Daulby Street, Liverpool L69 3GA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Crabb","sequence":"additional","affiliation":[{"name":"Cole Eye Institute, Cleveland Clinic, Cleveland, OH 44195, USA"},{"name":"Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA"},{"name":"Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1080\/17469899.2020.1785872","article-title":"Unpacking the genetic etiology of uveal melanoma","volume":"15","author":"Thorton","year":"2020","journal-title":"Expert Rev. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Collaborative Ocular Melanoma Study Group (2006). The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: V. Twelve-year mortality rates and prognostic factors: COMS report No. 28. Arch. Ophthalmol., 124, 1684\u20131693.","DOI":"10.1001\/archopht.124.12.1684"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1111\/j.1755-148X.2012.00979.x","article-title":"The genetics of uveal melanoma: An emerging framework for targeted therapy","volume":"25","author":"Harbour","year":"2012","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1002\/1097-0142(19931001)72:7<2219::AID-CNCR2820720725>3.0.CO;2-J","article-title":"Prognosis and treatment of disseminated uveal melanoma","volume":"72","author":"Kath","year":"1993","journal-title":"Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Collaborative Ocular Melanoma Study Group (1998). The Collaborative Ocular Melanoma Study (COMS) randomized trial of pre-enucleation radiation of large choroidal melanoma I: Characteristics of patients enrolled and not enrolled. COMS report no. 9. Am. J. Ophthalmol., 125, 767\u2013778.","DOI":"10.1016\/S0002-9394(98)00038-5"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.ajo.2009.07.004","article-title":"Molecular prognostic testing and individualized patient care in uveal melanoma","volume":"148","author":"Harbour","year":"2009","journal-title":"Am. J. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.mpdhp.2014.11.002","article-title":"An Update on Ocular Melanoma","volume":"21","author":"Kalirai","year":"2014","journal-title":"Diagn. Histopathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"360136","DOI":"10.1155\/2010\/360136","article-title":"Genetics of uveal melanoma and cutaneous melanoma: Two of a kind?","volume":"2010","author":"Kilic","year":"2010","journal-title":"Dermatol. Res. Pract."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s11912-017-0606-5","article-title":"Immunotherapy for the Treatment of Uveal Melanoma: Current Status and Emerging Therapies","volume":"19","author":"Komatsubara","year":"2017","journal-title":"Curr. Oncol. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1038\/nrc2256","article-title":"Models, mechanisms and clinical evidence for cancer dormancy","volume":"7","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1126\/science.1194472","article-title":"Frequent mutation of BAP1 in metastasizing uveal melanomas","volume":"330","author":"Harbour","year":"2010","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/nature07586","article-title":"Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi","volume":"457","author":"Bezrookove","year":"2009","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1056\/NEJMoa1000584","article-title":"Mutations in GNA11 in uveal melanoma","volume":"363","author":"Griewank","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4624","DOI":"10.18632\/oncotarget.6614","article-title":"Deep sequencing of uveal melanoma identifies a recurrent mutation in PLCB4","volume":"7","author":"Johansson","year":"2016","journal-title":"Oncotarget"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/ng.3549","article-title":"Recurrent activating mutations of G-protein-coupled receptor CYSLTR2 in uveal melanoma","volume":"48","author":"Moore","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"213.e3","DOI":"10.1016\/j.ophtha.2012.08.016","article-title":"Gene expressing profiling of iris melanomas","volume":"120","author":"Harbour","year":"2013","journal-title":"Ophthalmology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.exer.2013.09.005","article-title":"Proteomics in uveal melanoma","volume":"118","author":"Ramasamy","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1016\/j.ophtha.2007.06.012","article-title":"Cytogenetics of uveal melanoma: A 7-year clinical experience","volume":"114","author":"Damato","year":"2007","journal-title":"Ophthalmology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1167\/iovs.14-15250","article-title":"Skewed expression of the genes encoding epigenetic modifiers in high-risk uveal melanoma","volume":"56","author":"Herlihy","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/s41467-019-14256-1","article-title":"Single-cell analysis reveals new evolutionary complexity in uveal melanoma","volume":"11","author":"Durante","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1002\/path.5384","article-title":"Loss of BAP1 expression is associated with an immunosuppressive microenvironment in uveal melanoma, with implications for immunotherapy development","volume":"250","author":"Figueiredo","year":"2020","journal-title":"J. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Krishna, Y., Acha-Sagredo, A., Sabat-Pospiech, D., Kipling, N., Clarke, K., Figueiredo, C.R., Kalirai, H., and Coupland, S.E. (2020). Transcriptome Profiling Reveals New Insights into the Immune Microenvironment and Upregulation of Novel Biomarkers in Metastatic Uveal Melanoma. Cancers, 12.","DOI":"10.3390\/cancers12102832"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2923","DOI":"10.1158\/1078-0432.CCR-06-2383","article-title":"Loss of Heterozygosity of Chromosome 3 Detected with Single Nucleotide Polymorphisms Is Superior to Monosomy 3 for Predicting Metastasis in Uveal Melanoma","volume":"13","author":"Onken","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3331","DOI":"10.1167\/iovs.11-9027","article-title":"Chromosome 3 status in uveal melanoma: A comparison of fluorescence in situ hybridization and single-nucleotide polymorphism array","volume":"53","author":"Singh","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3048","DOI":"10.1167\/iovs.08-3165","article-title":"Multiplex ligation-dependent probe amplification of uveal melanoma: Correlation with metastatic death","volume":"50","author":"Damato","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"461","DOI":"10.2353\/jmoldx.2010.090220","article-title":"An accurate, clinically feasible multi-gene expression assay for predicting metastasis in uveal melanoma","volume":"12","author":"Onken","year":"2010","journal-title":"J. Mol. Diagn."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1016\/j.ophtha.2012.02.017","article-title":"Collaborative Ocular Oncology Group report number 1: Prospective validation of a multi-gene prognostic assay in uveal melanoma","volume":"119","author":"Onken","year":"2012","journal-title":"Ophthalmology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/978-1-62703-727-3_22","article-title":"A prognostic test to predict the risk of metastasis in uveal melanoma based on a 15-gene expression profile","volume":"1102","author":"Harbour","year":"2014","journal-title":"Methods Mol. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1016\/j.ophtha.2011.01.040","article-title":"Uveal melanoma: Trends in incidence, treatment, and survival","volume":"118","author":"Singh","year":"2011","journal-title":"Ophthalmology"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Thornton, S., Coupland, S.E., Olohan, L., Sibbring, J.S., Kenny, J.G., Hertz-Fowler, C., Liu, X., Haldenby, S., Heimann, H., and Hussain, R. (2020). Targeted Next-Generation Sequencing of 117 Routine Clinical Samples Provides Further Insights into the Molecular Landscape of Uveal Melanoma. Cancers, 12.","DOI":"10.3390\/cancers12041039"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1111\/aos.13580","article-title":"Genetic prognostication in uveal melanoma","volume":"96","author":"Dogrusoz","year":"2018","journal-title":"Acta Ophthalmol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Martel, A., Baillif, S., Nahon-Esteve, S., Gastaud, L., Bertolotto, C., Romeo, B., Mograbi, B., Lassalle, S., and Hofman, P. (2020). Liquid Biopsy for Solid Ophthalmic Malignancies: An Updated Review and Perspectives. Cancers, 12.","DOI":"10.3390\/cancers12113284"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Crabb, J.W., Hu, B., Crabb, J.S., Triozzi, P., Saunthararajah, Y., Tubbs, R., and Singh, A.D. (2015). iTRAQ Quantitative Proteomic Comparison of Metastatic and Non-Metastatic Uveal Melanoma Tumors. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0135543"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1167\/iovs.09-3913","article-title":"Proteomics of uveal melanomas suggests HSP-27 as a possible surrogate marker of chromosome 3 loss","volume":"51","author":"Coupland","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4634","DOI":"10.1167\/iovs.11-9019","article-title":"Differential expression of fourteen proteins between uveal melanoma from patients who subsequently developed distant metastases versus those who did Not","volume":"53","author":"Linge","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1097\/00008390-200312000-00013","article-title":"Proteomics in uveal melanoma","volume":"13","author":"Missotten","year":"2003","journal-title":"Melanoma Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4980","DOI":"10.1002\/pmic.200500030","article-title":"Proteome analysis of a human uveal melanoma primary cell culture by 2-DE and MS","volume":"5","author":"Pardo","year":"2005","journal-title":"Proteomics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1002\/ijc.21942","article-title":"The characterization of the invasion phenotype of uveal melanoma tumour cells shows the presence of MUC18 and HMG-1 metastasis markers and leads to the identification of DJ-1 as a potential serum biomarker","volume":"119","author":"Pardo","year":"2006","journal-title":"Int. J. Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2802","DOI":"10.1021\/pr070021t","article-title":"Biomarker discovery from uveal melanoma secretomes: Identification of gp100 and cathepsin D in patient serum","volume":"6","author":"Pardo","year":"2007","journal-title":"J. Proteome Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1167\/iovs.05-0314","article-title":"Proteomic analysis of uveal melanoma reveals novel potential markers involved in tumor progression","volume":"47","author":"Zuidervaart","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1093\/jrr\/rrt010","article-title":"Quantitative proteomic analysis for radiation-induced cell cycle suspension in 92-1 melanoma cell line","volume":"54","author":"Wang","year":"2013","journal-title":"J. Radiat. Res."},{"key":"ref_42","first-page":"286","article-title":"Proteomic analysis of energy metabolism and signal transduction in irradiated melanoma cells","volume":"6","author":"Yan","year":"2013","journal-title":"Int. J. Ophthalmol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"49623","DOI":"10.18632\/oncotarget.10418","article-title":"In-depth proteomic profiling of the uveal melanoma secretome","volume":"7","author":"Angi","year":"2016","journal-title":"Oncotarget"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Tsering, T., Laskaris, A., Abdouh, M., Bustamante, P., Parent, S., Jin, E., Ferrier, S.T., Arena, G., and Burnier, J.V. (2020). Uveal Melanoma-Derived Extracellular Vesicles Display Transforming Potential and Carry Protein Cargo Involved in Metastatic Niche Preparation. Cancers, 12.","DOI":"10.3390\/cancers12102923"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Guo, Z., Zhang, Y., Zou, L., Wang, D., Shao, C., Wang, Y., Sun, W., and Zhang, L. (2015). A Proteomic Analysis of Individual and Gender Variations in Normal Human Urine and Cerebrospinal Fluid Using iTRAQ Quantification. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0133270"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.1021\/acs.jproteome.5b00176","article-title":"Can \u201cnormal\u201d protein expression ranges be estimated with high-throughput proteomics?","volume":"14","author":"Higdon","year":"2015","journal-title":"J. Proteome Res."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Radivoyevitch, T., Zabor, E.C., and Singh, A.D. (2021). Uveal Melanoma: Long-Term Survival. PLoS ONE.","DOI":"10.1371\/journal.pone.0250939"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1001\/jamaophthalmol.2020.5720","article-title":"Estimating Cured Fractions of Uveal Melanoma","volume":"139","author":"Singh","year":"2021","journal-title":"JAMA Ophthalmol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.ccell.2017.07.003","article-title":"Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma","volume":"32","author":"Robertson","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1158\/0008-5472.CAN-10-0605","article-title":"High PTP4A3 phosphatase expression correlates with metastatic risk in uveal melanoma patients","volume":"71","author":"Laurent","year":"2011","journal-title":"Cancer Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1074\/mcp.M400055-MCP200","article-title":"Integrated genomic and proteomic analyses of gene expression in Mammalian cells","volume":"3","author":"Tian","year":"2004","journal-title":"Mol. Cell. Proteom."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1111\/j.1755-3768.2010.02038.x","article-title":"HSP-27 protein expression in uveal melanoma: Correlation with predicted survival","volume":"90","author":"Jmor","year":"2012","journal-title":"Acta Ophthalmol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/0198-8859(95)00083-G","article-title":"HLA antigen expression on uveal melanoma cells in vivo and in vitro","volume":"44","author":"Kool","year":"1995","journal-title":"Hum. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Gangemi, R., Mirisola, V., Barisione, G., Fabbi, M., Brizzolara, A., Lanza, F., Mosci, C., Salvi, S., Gualco, M., and Truini, M. (2012). Mda-9\/syntenin is expressed in uveal melanoma and correlates with metastatic progression. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0029989"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1007\/s10147-019-01519-6","article-title":"Prognostic relevance of ATM protein in uveal melanoma and its association with clinicopathological factors","volume":"24","author":"Jha","year":"2019","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3036","DOI":"10.1002\/cam4.2122","article-title":"DNA alteration-based classification of uveal melanoma gives better prognostic stratification than immune infiltration, which has a neutral effect in high-risk group","volume":"8","author":"Narasimhaiah","year":"2019","journal-title":"Cancer Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4187","DOI":"10.1167\/iovs.19-28082","article-title":"Elevated Endogenous SDHA Drives Pathological Metabolism in Highly Metastatic Uveal Melanoma","volume":"60","author":"Chattopadhyay","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s12014-019-9230-8","article-title":"A multiplex immunoassay of serum biomarkers for the detection of uveal melanoma","volume":"16","author":"Song","year":"2019","journal-title":"Clin. Proteom."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s12943-021-01336-4","article-title":"Liquid biopsy proteomics of uveal melanoma reveals biomarkers associated with metastatic risk","volume":"20","author":"Velez","year":"2021","journal-title":"Mol. Cancer"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.molimm.2013.11.018","article-title":"Circulating immune cell and microRNA in patients with uveal melanoma developing metastatic disease","volume":"58","author":"Achberger","year":"2014","journal-title":"Mol. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1097\/CMR.0000000000000207","article-title":"Spontaneous cellular and humoral tumor antigen responses in patients with uveal melanoma","volume":"25","author":"Triozzi","year":"2015","journal-title":"Melanoma Res."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Anand, K., Roszik, J., Gombos, D., Upshaw, J., Sarli, V., Meas, S., Lucci, A., Hall, C., and Patel, S. (2019). Pilot Study of Circulating Tumor Cells in Early-Stage and Metastatic Uveal Melanoma. Cancers, 11.","DOI":"10.3390\/cancers11060856"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Park, J.J., Diefenbacj, R.J., Byrne, N., Long, G.V., Scolyer, R.A., Gray, E.S., Carlino, M.S., and Rizos, H. (2021). Circulating tumor DNA Reflects Uveal Melanoma Responses to Protei Kinase C Inhibition. Cancers, 13.","DOI":"10.3390\/cancers13071740"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Williams, P.S., Moore, L.R., Joshi, P., Goodin, M., Zborowski, M., and Fleischman, A. (2021). Microfluidic chip for graduated magnetic separation of circulating tumor cells by their epithelial cell adhesion molecule expression and magnetic nanoparticle binding. J. Chromatogr. A, 1637.","DOI":"10.1016\/j.chroma.2020.461823"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/0003-2697(85)90442-7","article-title":"Measurements of protein using bicinchoninoc acid","volume":"150","author":"Smith","year":"1985","journal-title":"Anal. Biochem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1074\/mcp.M700525-MCP200","article-title":"Retinal pigment epithelium lipofuscin proteomics","volume":"7","author":"Ng","year":"2008","journal-title":"Mol. Cell. Proteom."},{"key":"ref_67","unstructured":"Crabb, J.W., West, K.A., Dodson, W.S., and Hulmes, J.D. (2001). Amino Acid Analysis. Current Protocols in Protein Science, John Wiley & Sons, Inc."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"16717","DOI":"10.1038\/s41598-020-73686-w","article-title":"Quantitative proteomic comparison of myofibroblasts derived from bone marrow and cornea","volume":"10","author":"Saikia","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1074\/mcp.M900523-MCP200","article-title":"Quantitative proteomics: Comparison of the macular Bruch membrane\/choroid complex from age-related macular degeneration and normal eyes","volume":"9","author":"Yuan","year":"2010","journal-title":"Mol. Cell. Proteom."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"8287","DOI":"10.1167\/iovs.11-8218","article-title":"Quantitative Proteomics: TGF-\u03b22-Signaling in Trabecular Meshwork Cells","volume":"52","author":"Bollinger","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_71","first-page":"2001","article-title":"Dexamethasone-Induced Proteomic Changes in Trabecular Meshwork Cells: Insights to the Molecular Basis of Steroid-Induced Glaucoma","volume":"18","author":"Bollinger","year":"2012","journal-title":"Mol. Vis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1074\/mcp.M112.021592","article-title":"Defining, comparing, and improving iTRAQ quantification in mass spectrometry proteomics data","volume":"12","author":"Forshed","year":"2013","journal-title":"Mol. Cell. Proteom."},{"key":"ref_73","unstructured":"R-Development-Team (2019). R: A Language and Environment for Statistical Computing, R-Development-Team. R version 3.6.3."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"Limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_75","first-page":"D498","article-title":"The reactome pathway knowledgebase","volume":"48","author":"Jassal","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4644","DOI":"10.1158\/1078-0432.CCR-19-0173","article-title":"The Immune Microenvironment in Hormone Receptor-Positive Breast Cancer Before and After Preoperative Chemotherapy","volume":"25","author":"Waks","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1074\/mcp.M800453-MCP200","article-title":"Assessing susceptibility to age-related macular degeneration with proteomic and genomic biomarkers","volume":"8","author":"Gu","year":"2009","journal-title":"Mol. Cell. Proteom."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1021\/pr1011476","article-title":"Coomassie staining as loading control in Western blot analysis","volume":"10","author":"Welinder","year":"2011","journal-title":"J. Proteome Res."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/14\/3520\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:30:21Z","timestamp":1760164221000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/14\/3520"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,14]]},"references-count":78,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["cancers13143520"],"URL":"https:\/\/doi.org\/10.3390\/cancers13143520","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,14]]}}}