The Analysis of Inflammation-Related Proteins in a Cargo of Exosomes Derived from the Serum of Uveal Melanoma Patients Reveals Potential Biomarkers of Disease Progression
Status PubMed-not-MEDLINE Language English Country Switzerland Media electronic
Document type Journal Article
Grant support
DEC-2018/02/X/NZ5/02659
National Science Center
CZ.02.2.69/0.0/0.0/18_053/0016976
OP RDE project "International mobility of research, technical and administrative workers of re-search organizations"
PubMed
34283046
PubMed Central
PMC8268237
DOI
10.3390/cancers13133334
PII: cancers13133334
Knihovny.cz E-resources
- Keywords
- biomarkers, exosomes, inflammation-related proteins, uveal melanoma,
- Publication type
- Journal Article MeSH
BACKGROUND: Uveal melanoma (UM) is the most common intraocular tumour in adults with a poor prognosis and extremely high mortality rate due to the development of metastatic disease. However, despite relatively good knowledge about the histological and genetic risk factors for metastasis development, there is no specific biomarker that would allow early detection of UM progression. Recently, exosomes and their molecular cargo have been widely studied in the search for potential biomarkers in several cancers. The purpose of this study was to analyze the inflammation-related protein cargo of exosomes derived from the serum of primary and metastatic UM patients and healthy donors. METHODS: The exosomes were isolated from the serum of primary and metastatic UM patients and healthy donors. Using multiplex immunoassay technology, we analyzed the concentration of 37 inflammation-related proteins in obtained exosomes. RESULTS: The analysis of protein cargo showed several molecules related to inflammation, such as interferon-gamma, interleukin 2, 22 and 12(p40), Pentraxin-3, TNFSF13B and TNFSF8 which were significantly enriched in metastatic UM exosomes. We showed a significant correlation between the disease stage and the concentration of these inflammation-related proteins from exosomal cargo. CONCLUSIONS: Based on the obtained results, we propose the panel of exosomal proteins for early detection of uveal melanoma progression into metastatic disease.
Department of Cell Biology Faculty of Science Charles University BIOCEV 25150 Vestec Czech Republic
Department of Chemotherapy Greater Poland Cancer Centre 61 866 Poznan Poland
Department of Electroradiology Poznan University of Medical Sciences 61 866 Poznan Poland
Department of Tumor Pathology Greater Poland Cancer Centre 61 866 Poznan Poland
Radiobiology Lab Department of Medical Physics Greater Poland Cancer 61 866 Poznan Poland
See more in PubMed
Berus T., Halon A., Markiewicz A., Orlowska-Heitzman J., Romanowska-Dixon B., Donizy P. Clinical, Histopathological and Cytogenetic Prognosticators in Uveal Melanoma—A Comprehensive Review. Anticancer Res. 2017;37:6541–6549. doi: 10.21873/anticanres.12110. PubMed DOI
Jager M.J., Shields C.L., Cebulla C.M., Abdel-Rahman M.H., Grossniklaus H.E., Stern M.H., Carvajal R.D., Belfort R.N., Jia R., Shields J.A., et al. Uveal melanoma. Nat. Rev. Dis. Primers. 2020;6:24. doi: 10.1038/s41572-020-0158-0. PubMed DOI
Robertson A.G., Shih J., Yau C., Gibb E.A., Oba J., Mungall K.L., Hess J.M., Uzunangelov V., Walter V., Danilova L., et al. Integrative Analysis Identifies Four Molecular and Clinical Subsets in Uveal Melanoma. Cancer Cell. 2017;32:204–220.e215. doi: 10.1016/j.ccell.2017.07.003. PubMed DOI PMC
Krantz B.A., Dave N., Komatsubara K.M., Marr B.P., Carvajal R.D. Uveal melanoma: Epidemiology, etiology, and treatment of primary disease. Clin. Ophthalmol. 2017;11:279–289. doi: 10.2147/OPTH.S89591. PubMed DOI PMC
Ortega M.A., Fraile-Martínez O., García-Honduvilla N., Coca S., Álvarez-Mon M., Buján J., Teus M.A. Update on uveal melanoma: Translational research from biology to clinical practice (Review) Int. J. Oncol. 2020;57:1262–1279. doi: 10.3892/ijo.2020.5140. PubMed DOI PMC
Damato B. Ocular treatment of choroidal melanoma in relation to the prevention of metastatic death—A personal view. Prog. Retin. Eye Res. 2018;66:187–199. doi: 10.1016/j.preteyeres.2018.03.004. PubMed DOI
Kaliki S., Shields C.L. Uveal melanoma: Relatively rare but deadly cancer. Eye. 2017;31:241–257. doi: 10.1038/eye.2016.275. PubMed DOI PMC
Terai M., Mu Z., Eschelman D.J., Gonsalves C.F., Kageyama K., Chervoneva I., Orloff M., Weight R., Mastrangelo M.J., Cristofanilli M., et al. Arterial Blood, Rather Than Venous Blood, is a Better Source for Circulating Melanoma Cells. EBioMedicine. 2015;2:1821–1826. doi: 10.1016/j.ebiom.2015.09.019. PubMed DOI PMC
Schuster R., Bechrakis N.E., Stroux A., Busse A., Schmittel A., Thiel E., Foerster M.H., Keilholz U. Prognostic relevance of circulating tumor cells in metastatic uveal melanoma. Oncology. 2011;80:57–62. doi: 10.1159/000328283. PubMed DOI
Tura A., Merz H., Reinsberg M., Lüke M., Jager M.J., Grisanti S., Lüke J. Analysis of monosomy-3 in immunomagnetically isolated circulating melanoma cells in uveal melanoma patients. Pigment. Cell Melanoma Res. 2016;29:583–589. doi: 10.1111/pcmr.12507. PubMed DOI
Bidard F.C., Madic J., Mariani P., Piperno-Neumann S., Rampanou A., Servois V., Cassoux N., Desjardins L., Milder M., Vaucher I., et al. Detection rate and prognostic value of circulating tumor cells and circulating tumor DNA in metastatic uveal melanoma. Int. J. Cancer. 2014;134:1207–1213. doi: 10.1002/ijc.28436. PubMed DOI
Achberger S., Aldrich W., Tubbs R., Crabb J.W., Singh A.D., Triozzi P.L. Circulating immune cell and microRNA in patients with uveal melanoma developing metastatic disease. Mol. Immunol. 2014;58:182–186. doi: 10.1016/j.molimm.2013.11.018. PubMed DOI PMC
Russo A., Caltabiano R., Longo A., Avitabile T., Franco L.M., Bonfiglio V., Puzzo L., Reibaldi M. Increased Levels of miRNA-146a in Serum and Histologic Samples of Patients with Uveal Melanoma. Front Pharmacol. 2016;7:424. doi: 10.3389/fphar.2016.00424. PubMed DOI PMC
Stark M.S., Gray E.S., Isaacs T., Chen F.K., Millward M., McEvoy A., Zaenker P., Ziman M., Soyer H.P., Glasson W.J., et al. A Panel of Circulating MicroRNAs Detects Uveal Melanoma With High Precision. Transl. Vis. Sci. Technol. 2019;8:12. doi: 10.1167/tvst.8.6.12. PubMed DOI PMC
Haritoglou I., Wolf A., Maier T., Haritoglou C., Hein R., Schaller U.C. Osteopontin and ’melanoma inhibitory activity’: Comparison of two serological tumor markers in metastatic uveal melanoma patients. Ophthalmologica. 2009;223:239–243. doi: 10.1159/000206139. PubMed DOI
Barak V., Frenkel S., Kalickman I., Maniotis A.J., Folberg R., Pe’er J. Serum markers to detect metastatic uveal melanoma. Anticancer Res. 2007;27:1897–1900. PubMed PMC
Barisione G., Fabbi M., Gino A., Queirolo P., Orgiano L., Spano L., Picasso V., Pfeffer U., Mosci C., Jager M.J., et al. Potential Role of Soluble c-Met as a New Candidate Biomarker of Metastatic Uveal Melanoma. JAMA Ophthalmol. 2015;133:1013–1021. doi: 10.1001/jamaophthalmol.2015.1766. PubMed DOI
Velez G., Nguyen H.V., Chemudupati T., Ludwig C.A., Toral M., Reddy S., Mruthyunjaya P., Mahajan V.B. Liquid biopsy proteomics of uveal melanoma reveals biomarkers associated with metastatic risk. Mol. Cancer. 2021;20:39. doi: 10.1186/s12943-021-01336-4. PubMed DOI PMC
Reiniger I.W., Schaller U.C., Haritoglou C., Hein R., Bosserhoff A.K., Kampik A., Mueller A.J. “Melanoma inhibitory activity” (MIA): A promising serological tumour marker in metastatic uveal melanoma. Graefes Arch. Clin. Exp. Ophthalmol. 2005;243:1161–1166. doi: 10.1007/s00417-005-1171-4. PubMed DOI
An T., Qin S., Xu Y., Tang Y., Huang Y., Situ B., Inal J.M., Zheng L. Exosomes serve as tumour markers for personalized diagnostics owing to their important role in cancer metastasis. J. Extracell. Vesicles. 2015;4:27522. doi: 10.3402/jev.v4.27522. PubMed DOI PMC
Alegre E., Zubiri L., Perez-Gracia J.L., González-Cao M., Soria L., Martín-Algarra S., González A. Circulating melanoma exosomes as diagnostic and prognosis biomarkers. Clin. Chim. Acta. 2016;454:28–32. doi: 10.1016/j.cca.2015.12.031. PubMed DOI
Szajnik M., Derbis M., Lach M., Patalas P., Michalak M., Drzewiecka H., Szpurek D., Nowakowski A., Spaczynski M., Baranowski W., et al. Exosomes in Plasma of Patients with Ovarian Carcinoma: Potential Biomarkers of Tumor Progression and Response to Therapy. Gynecol. Obstet. 2013;3(Suppl.4) doi: 10.4172/2161-0932.S4-003. PubMed DOI PMC
Khan S., Jutzy J.M., Valenzuela M.M., Turay D., Aspe J.R., Ashok A., Mirshahidi S., Mercola D., Lilly M.B., Wall N.R. Plasma-derived exosomal survivin, a plausible biomarker for early detection of prostate cancer. PLoS ONE. 2012;7:e46737. doi: 10.1371/journal.pone.0046737. PubMed DOI PMC
Tsering T., Laskaris A., Abdouh M., Bustamante P., Parent S., Jin E., Ferrier S.T., Arena G., Burnier J.V. Uveal Melanoma-Derived Extracellular Vesicles Display Transforming Potential and Carry Protein Cargo Involved in Metastatic Niche Preparation. Cancers. 2020;12:2923. doi: 10.3390/cancers12102923. PubMed DOI PMC
Surman M., Hoja-Łukowicz D., Szwed S., Kędracka-Krok S., Jankowska U., Kurtyka M., Drożdż A., Lityńska A., Stępień E., Przybyło M. An Insight into the Proteome of Uveal Melanoma-Derived Ectosomes Reveals the Presence of Potentially Useful Biomarkers. Int. J. Mol. Sci. 2019;20:3789. doi: 10.3390/ijms20153789. PubMed DOI PMC
Théry C., Witwer K.W., Aikawa E., Alcaraz M.J., Anderson J.D., Andriantsitohaina R., Antoniou A., Arab T., Archer F., Atkin-Smith G.K., et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J. Extracell. Vesicles. 2018;7:1535750. doi: 10.1080/20013078.2018.1535750. PubMed DOI PMC
Kulcenty K., Piotrowski I., Wroblewska J.P., Wasiewicz J., Suchorska A.W.M. The Composition of Surgical Wound Fluids from Breast Cancer Patients is Affected by Intraoperative Radiotherapy Treatment and Depends on the Molecular Subtype of Breast Cancer. Cancers. 2019;12:11. doi: 10.3390/cancers12010011. PubMed DOI PMC
Zhao Y., Weber S.R., Lease J., Russo M., Siedlecki C.A., Xu L.C., Chen H., Wang W., Ford M., Simó R., et al. Liquid Biopsy of Vitreous Reveals an Abundant Vesicle Population Consistent With the Size and Morphology of Exosomes. Transl. Vis. Sci. Technol. 2018;7:6. doi: 10.1167/tvst.7.3.6. PubMed DOI PMC
Ragusa M., Barbagallo C., Statello L., Caltabiano R., Russo A., Puzzo L., Avitabile T., Longo A., Toro M.D., Barbagallo D., et al. MiRNA profiling in vitreous humor, vitreal exosomes and serum from uveal melanoma patients: Pathological and diagnostic implications. Cancer Biol. Ther. 2015;16:1387–1396. doi: 10.1080/15384047.2015.1046021. PubMed DOI PMC
Eldh M., Olofsson Bagge R., Lässer C., Svanvik J., Sjöstrand M., Mattsson J., Lindnér P., Choi D.S., Gho Y.S., Lötvall J. MicroRNA in exosomes isolated directly from the liver circulation in patients with metastatic uveal melanoma. BMC Cancer. 2014;14:962. doi: 10.1186/1471-2407-14-962. PubMed DOI PMC
Angi M., Kalirai H., Prendergast S., Simpson D., Hammond D.E., Madigan M.C., Beynon R.J., Coupland S.E. In-depth proteomic profiling of the uveal melanoma secretome. Oncotarget. 2016;7:49623–49635. doi: 10.18632/oncotarget.10418. PubMed DOI PMC
Piotrowski I., Kulcenty K., Suchorska W. Interplay between inflammation and cancer. Rep. Pract. Oncol. Radiother. 2020;25:422–427. doi: 10.1016/j.rpor.2020.04.004. PubMed DOI PMC
Greten F.R., Grivennikov S.I. Inflammation and Cancer: Triggers, Mechanisms, and Consequences. Immunity. 2019;51:27–41. doi: 10.1016/j.immuni.2019.06.025. PubMed DOI PMC
Brocker C., Thompson D., Matsumoto A., Nebert D.W., Vasiliou V. Evolutionary divergence and functions of the human interleukin (IL) gene family. Hum. Genom. 2010;5:30–55. doi: 10.1186/1479-7364-5-1-30. PubMed DOI PMC
Setrerrahmane S., Xu H. Tumor-related interleukins: Old validated targets for new anti-cancer drug development. Mol. Cancer. 2017;16:153. doi: 10.1186/s12943-017-0721-9. PubMed DOI PMC
Lee C.S., Jun I.H., Kim T.I., Byeon S.H., Koh H.J., Lee S.C. Expression of 12 cytokines in aqueous humour of uveal melanoma before and after combined Ruthenium-106 brachytherapy and transpupillary thermotherapy. Acta Ophthalmol. 2012;90:e314–e320. doi: 10.1111/j.1755-3768.2012.02392.x. PubMed DOI
Dunavoelgyi R., Funk M., Sacu S., Georgopoulos M., Zlabinger G., Zehetmayer M., Schmidt-Erfurth U. Intraocular activation of angiogenic and inflammatory pathways in uveal melanoma. Retina. 2012;32:1373–1384. doi: 10.1097/IAE.0b013e318239e299. PubMed DOI
Nagarkatti-Gude N., Bronkhorst I.H., van Duinen S.G., Luyten G.P., Jager M.J. Cytokines and chemokines in the vitreous fluid of eyes with uveal melanoma. Invest. Ophthalmol. Vis. Sci. 2012;53:6748–6755. doi: 10.1167/iovs.12-10123. PubMed DOI
Masaoutis C., Kokkali S., Theocharis S. Immunotherapy in uveal melanoma: Novel strategies and opportunities for personalized treatment. Expert Opin. Investig. Drugs. 2021;30:555–569. doi: 10.1080/13543784.2021.1898587. PubMed DOI
Nishina T., Deguchi Y., Ohshima D., Takeda W., Ohtsuka M., Shichino S., Ueha S., Yamazaki S., Kawauchi M., Nakamura E., et al. Interleukin-11-expressing fibroblasts have a unique gene signature correlated with poor prognosis of colorectal cancer. Nat. Commun. 2021;12:2281. doi: 10.1038/s41467-021-22450-3. PubMed DOI PMC
Tao L., Huang G., Wang R., Pan Y., He Z., Chu X., Song H., Chen L. Cancer-associated fibroblasts treated with cisplatin facilitates chemoresistance of lung adenocarcinoma through IL-11/IL-11R/STAT3 signaling pathway. Sci. Rep. 2016;6:38408. doi: 10.1038/srep38408. PubMed DOI PMC
Johnstone C.N., Chand A., Putoczki T.L., Ernst M. Emerging roles for IL-11 signaling in cancer development and progression: Focus on breast cancer. Cytokine Growth Factor Rev. 2015;26:489–498. doi: 10.1016/j.cytogfr.2015.07.015. PubMed DOI
Putoczki T.L., Ernst M. IL-11 signaling as a therapeutic target for cancer. Immunotherapy. 2015;7:441–453. doi: 10.2217/imt.15.17. PubMed DOI
Fang S., Wang Y., Chun Y.S., Liu H., Ross M.I., Gershenwald J.E., Cormier J.N., Royal R.E., Lucci A., Schacherer C.W., et al. The relationship between blood IL-12p40 level and melanoma progression. Int. J. Cancer. 2015;136:1874–1880. doi: 10.1002/ijc.29182. PubMed DOI PMC
Cooper A.M., Khader S.A. IL-12p40: An inherently agonistic cytokine. Trends Immunol. 2007;28:33–38. doi: 10.1016/j.it.2006.11.002. PubMed DOI
Tugues S., Burkhard S.H., Ohs I., Vrohlings M., Nussbaum K., Vom Berg J., Kulig P., Becher B. New insights into IL-12-mediated tumor suppression. Cell Death Differ. 2015;22:237–246. doi: 10.1038/cdd.2014.134. PubMed DOI PMC
Bisevac J.P., Stanojevic I., Mijuskovic Z., Banovic T., Djukic M., Vojvodic D. High Interleukin 27 Production is Associated with Early Clinical Stage and Localized Disease in Patients with Melanoma. J. Med. Biochem. 2016;35:443–450. doi: 10.1515/jomb-2016-0018. PubMed DOI PMC
Yoshimoto T., Morishima N., Mizoguchi I., Shimizu M., Nagai H., Oniki S., Oka M., Nishigori C., Mizuguchi J. Antiproliferative activity of IL-27 on melanoma. J. Immunol. 2008;180:6527–6535. doi: 10.4049/jimmunol.180.10.6527. PubMed DOI
Fabbi M., Carbotti G., Ferrini S. Dual Roles of IL-27 in Cancer Biology and Immunotherapy. Mediat. Inflamm. 2017;2017:3958069. doi: 10.1155/2017/3958069. PubMed DOI PMC
Lane A.M., Egan K.M., Harmon D., Holbrook A., Munzenrider J.E., Gragoudas E.S. Adjuvant interferon therapy for patients with uveal melanoma at high risk of metastasis. Ophthalmology. 2009;116:2206–2212. doi: 10.1016/j.ophtha.2009.04.044. PubMed DOI
Nathan F.E., Berd D., Sato T., Shield J.A., Shields C.L., De Potter P., Mastrangelo M.J. BOLD+interferon in the treatment of metastatic uveal melanoma: First report of active systemic therapy. J. Exp. Clin. Cancer Res. 1997;16:201–208. PubMed
Qin Y., Bollin K., de Macedo M.P., Carapeto F., Kim K.B., Roszik J., Wani K.M., Reuben A., Reddy S.T., Williams M.D., et al. Immune profiling of uveal melanoma identifies a potential signature associated with response to immunotherapy. J. Immunother. Cancer. 2020;8:e000960. doi: 10.1136/jitc-2020-000960. PubMed DOI PMC
Song J., Merbs S.L., Sokoll L.J., Chan D.W., Zhang Z. A multiplex immunoassay of serum biomarkers for the detection of uveal melanoma. Clin. Proteomics. 2019;16:10. doi: 10.1186/s12014-019-9230-8. PubMed DOI PMC
Damento G.M., Pulido J.S., Abbott B.A., Hodge D.O., Dalvin L.A. TNF-Alpha Inhibition and Other Immunosuppressants in the Development of Uveal and Cutaneous Melanoma. Mayo Clin. Proc. 2019;94:1287–1295. doi: 10.1016/j.mayocp.2018.11.033. PubMed DOI
Montfort A., Colacios C., Levade T., Andrieu-Abadie N., Meyer N., Ségui B. The TNF Paradox in Cancer Progression and Immunotherapy. Front. Immunol. 2019;10:1818. doi: 10.3389/fimmu.2019.01818. PubMed DOI PMC
Lejeune F.J., Liénard D., Matter M., Rüegg C. Efficiency of recombinant human TNF in human cancer therapy. Cancer Immun. 2006;6:6. PubMed
Cai X., Cao C., Li J., Chen F., Zhang S., Liu B., Zhang W., Zhang X., Ye L. Inflammatory factor TNF-α promotes the growth of breast cancer via the positive feedback loop of TNFR1/NF-κB (and/or p38)/p-STAT3/HBXIP/TNFR1. Oncotarget. 2017;8:58338–58352. doi: 10.18632/oncotarget.16873. PubMed DOI PMC
Rossi S., Cordella M., Tabolacci C., Nassa G., D’Arcangelo D., Senatore C., Pagnotto P., Magliozzi R., Salvati A., Weisz A., et al. TNF-alpha and metalloproteases as key players in melanoma cells aggressiveness. J. Exp. Clin. Cancer Res. 2018;37:326. doi: 10.1186/s13046-018-0982-1. PubMed DOI PMC
Liu W., Lu X., Shi P., Yang G., Zhou Z., Li W., Mao X., Jiang D., Chen C. TNF-α increases breast cancer stem-like cells through up-regulating TAZ expression via the non-canonical NF-κB pathway. Sci. Rep. 2020;10:1804. doi: 10.1038/s41598-020-58642-y. PubMed DOI PMC
Damento G., Kavoussi S.C., Materin M.A., Salomão D.R., Quiram P.A., Balasubramaniam S., Pulido J.S. Clinical and histologic findings in patients with uveal melanomas after taking tumor necrosis factor-α inhibitors. Mayo Clin. Proc. 2014;89:1481–1486. doi: 10.1016/j.mayocp.2014.08.012. PubMed DOI
Taha E.A., Sogawa C., Okusha Y., Kawai H., Oo M.W., Elseoudi A., Lu Y., Nagatsuka H., Kubota S., Satoh A., et al. Knockout of MMP3 Weakens Solid Tumor Organoids and Cancer Extracellular Vesicles. Cancers. 2020;12:1260. doi: 10.3390/cancers12051260. PubMed DOI PMC
Giacomini A., Ghedini G.C., Presta M., Ronca R. Long pentraxin 3: A novel multifaceted player in cancer. Biochim. Biophys. Acta Rev. Cancer. 2018;1869:53–63. doi: 10.1016/j.bbcan.2017.11.004. PubMed DOI
Rathore M., Girard C., Ohanna M., Tichet M., Ben Jouira R., Garcia E., Larbret F., Gesson M., Audebert S., Lacour J.P., et al. Cancer cell-derived long pentraxin 3 (PTX3) promotes melanoma migration through a toll-like receptor 4 (TLR4)/NF-κB signaling pathway. Oncogene. 2019;38:5873–5889. doi: 10.1038/s41388-019-0848-9. PubMed DOI
Coppola D., Szabo M., Boulware D., Muraca P., Alsarraj M., Chambers A.F., Yeatman T.J. Correlation of osteopontin protein expression and pathological stage across a wide variety of tumor histologies. Clin. Cancer Res. 2004;10:184–190. doi: 10.1158/1078-0432.CCR-1405-2. PubMed DOI
El-Tanani M.K., Yuen H.F., Shi Z., Platt-Higgins A., Buckley N.E., Mullan P.B., Harkin D.P., Johnston P.G., Rudland P.S. Osteopontin can act as an effector for a germline mutation of BRCA1 in malignant transformation of breast cancer-related cells. Cancer Sci. 2010;101:1354–1360. doi: 10.1111/j.1349-7006.2010.01561.x. PubMed DOI PMC
Pass H.I., Lott D., Lonardo F., Harbut M., Liu Z., Tang N., Carbone M., Webb C., Wali A. Asbestos exposure, pleural mesothelioma, and serum osteopontin levels. N. Engl. J. Med. 2005;353:1564–1573. doi: 10.1056/NEJMoa051185. PubMed DOI
Kadkol S.S., Lin A.Y., Barak V., Kalickman I., Leach L., Valyi-Nagy K., Majumdar D., Setty S., Maniotis A.J., Folberg R., et al. Osteopontin expression and serum levels in metastatic uveal melanoma: A pilot study. Investig. Ophthalmol. Vis. Sci. 2006;47:802–806. doi: 10.1167/iovs.05-0422. PubMed DOI PMC
Song J., Zhang Z., Chan D.W. Detection of Uveal Melanoma by Multiplex Immunoassays of Serum Biomarkers. Methods Mol. Biol. 2021;2265:447–459. doi: 10.1186/s12014-019-9230-8. PubMed DOI
Wróblewska J.P., Lach M.S., Ustaszewski A., Kulcenty K., Ibbs M., Jagiełło I., Suchorska W.M., Marszałek A. The Potential Role of Selected miRNA in Uveal Melanoma Primary Tumors as Early Biomarkers of Disease Progression. Genes. 2020;11:271. doi: 10.3390/genes11030271. PubMed DOI PMC
Fitzgerald W., Freeman M.L., Lederman M.M., Vasilieva E., Romero R., Margolis L. A System of Cytokines Encapsulated in ExtraCellular Vesicles. Sci. Rep. 2018;8:8973. doi: 10.1038/s41598-018-27190-x. PubMed DOI PMC
Takov K., Yellon D.M., Davidson S.M. Comparison of small extracellular vesicles isolated from plasma by ultracentrifugation or size-exclusion chromatography: Yield, purity and functional potential. J. Extracell. Vesicles. 2019;8:1560809. doi: 10.1080/20013078.2018.1560809. PubMed DOI PMC