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Exploring the role of BAFF as biomarker in the detection of uveal melanoma metastases

  • Original Article – Cancer Research
  • Published:
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Abstract

Purpose

While B-cell activating factor (BAFF) was identified to promote the invasion in other malignancies, its role in the progression of uveal melanoma (UM) still remains unexplored. Here, we analysed the serum level of BAFF in UM patients with regard to its significance as biomarker for the metastases.

Methods

In this retrospective study, serum BAFF levels in 173 UM patients (36 with metastases and 137 without), and 23 healthy controls were measured with a multiplexed sandwich ELISA system and then correlated with clinicopathological characteristics such as primary tumor size, tumor location, histological cell type, sex, cancer stage, cytogenetic alterations of chromosome 3, and the metastatic burden. Immunohistochemical staining of 50 UM tissue specimens was also performed to evaluate the expression of BAFF and its receptors BAFF-R and TACI.

Results

The metastatic patients were identified to have significantly higher serum BAFF levels (mean ± SD, 1520.8 ± 1182.1 pg/ml) than those without metastases (950.4 ± 494.6 pg/ml) and controls (810.3 ± 140.5 pg/ml). While no distinctions were detected with regard to tumor location, histological cell type, gender, and monosomy 3, the patients in cancer stages II, III, and IV displayed higher serum BAFF levels than those in stage I. The serum BAFF level was significantly correlated with the metastatic burden. The serum BAFF level of 1120 pg/ml was identified to have the best performance for distinguishing the metastatic patients from non-metastatic patients. In the kinetic study, we noticed that 20.8% of the analysed patients already demonstrated elevated serum BAFF concentrations before the clinical diagnosis of metastases. Positive BAFF staining was detected in the cytoplasm of single tumor cells (in 13 specimens), macrophages (in 12 specimens), and tumor-infiltrating lymphocytes (TILs) (in 13 specimens). The expressions of BAFF-R and TACI were also observed in 17 and 36 of the 50 tested UM specimens, respectively.

Conclusions

Our study first suggests that BAFF might be a promising serum marker for the detection of UM metastases.

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Availability of data and materials

All relevant data were included in this manuscript and its supplementary materials.

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References

  • Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, Gershenwald JE, Compton CC, Hess KR, Sullivan DC, Jessup JM, Brierley JD, Gaspar LE, Schilsky RL, Balch CM, Winchester DP, Asare EA, Madera M, Gress DM, Meyer LR (2017) AJCC cancer staging manual. Springer, Switzerland

    Google Scholar 

  • Bakalian S, Marshall J-C, Logan P, Faingold D, Maloney S, di Cesare S, Martins C, Fernandes BF, Burnier MN (2008) Molecular pathways mediating liver metastasis in patients with uveal melanoma. Clin Cancer Res 14:951

    CAS  PubMed  Google Scholar 

  • Barak V, Frenkel S, Kalickman I, Maniotis AJ, Folberg R, Pe’Er J (2007) Serum markers to detect metastatic uveal melanoma. Anticancer Res 27:1897–1900

    CAS  PubMed  PubMed Central  Google Scholar 

  • Barak V, Kaiserman I, Frenkel S, Hendler K, Kalickman I, Pe’Er J (2011) The dynamics of serum tumor markers in predicting metastatic uveal melanoma (part 1). Anticancer Res 31:345–349

    CAS  PubMed  Google Scholar 

  • Berus T, Halon A, Markiewicz A, Orlowska-Heitzman J, Romanowska-Dixon B, Donizy P (2017) Clinical, histopathological and cytogenetic prognosticators in uveal melanoma—a comprehensive review. Anticancer Res 37:6541–6549

    CAS  PubMed  Google Scholar 

  • Bolkun L, Lemancewicz D, Jablonska E, Kulczynska A, Bolkun-Skornicka U, Kloczko J, Dzieciol J (2014) BAFF and APRIL as TNF superfamily molecules and angiogenesis parallel progression of human multiple myeloma. Ann Hematol 93:635–644

    CAS  PubMed  Google Scholar 

  • Bronkhorst IHG, Ly LV, Jordanova ES, Vrolijk J, Versluis M, Luyten GPM, Jager MJ (2011) Detection of M2-macrophages in uveal melanoma and relation with survival. Invest Ophthalmol Vis Sci 52:643–650

    PubMed  Google Scholar 

  • Bronkhorst IHG, Vu THK, Jordanova ES, Luyten GPM, Burg SHVD, Jager MJ (2012) Different subsets of tumor-infiltrating lymphocytes correlate with macrophage influx and monosomy 3 in uveal melanomatumor-infiltrating lymphocytes in uveal melanoma. Invest Ophthalmol Vis Sci 53:5370–5378

    CAS  PubMed  Google Scholar 

  • Brown J, Rathbone E, Hinsley S, Gregory W, Gossiel F, Marshall H, Burkinshaw R, Shulver H, Thandar H, Bertelli G, Maccon K, Bowman A, Hanby A, Bell R, Cameron D, Coleman R (2018) Associations between serum bone biomarkers in early breast cancer and development of bone metastasis: results from the AZURE (BIG01/04) trial. JNCI 110:871–879

    PubMed  PubMed Central  Google Scholar 

  • Carvajal RD, Schwartz GK, Tezel T, Marr B, Francis JH, Nathan PD (2017) Metastatic disease from uveal melanoma: treatment options and future prospects. Br J Ophthalmol 101:38–44

    PubMed  Google Scholar 

  • Chattopadhyay C, Kim DW, Gombos DS, Oba J, Qin Y, Williams MD, Esmaeli B, Grimm EA, Wargo JA, Woodman SE, Patel SP (2016) Uveal melanoma: From diagnosis to treatment and the science in between. Cancer 122:2299–2312

    PubMed  Google Scholar 

  • Chereches G, Barbos O, Buiga R, Balacescu O, Iancu D, Todor N, Balacescu L, Miron N, Bejinariu N, Ciuleanu T-EJJOBOOJOTBUOO (2017) Biomarkers for the early detection of relapses in metastatic colorectal cancers. J BUON 22:658–666

    PubMed  Google Scholar 

  • Clark WH Jr, Elder DE, Guerry D IV, Braitman LE, Trock BJ, Schultz D, Synnestvedt M, Halpern AC (1989) Model predicting survival in stage I melanoma based on tumor progression. JNCI 81:1893–1904

    PubMed  Google Scholar 

  • Coupland SE, Thornton S, Kalirai H (2020) Importance of partial losses of chromosome 3 in uveal melanoma in the BAP1 gene region. JAMA Ophthalmol 138:188–189

    PubMed  Google Scholar 

  • Damato B, Duke C, Coupland SE, Hiscott P, Smith PA, Campbell I, Douglas A, Howard P (2007) Cytogenetics of uveal melanoma: a 7-year clinical experience. Ophthalmology 114:1925–1931

    PubMed  Google Scholar 

  • Dogrusöz M, Bagger M, van Duinen SG, Kroes WG, Ruivenkamp CAL, Böhringer S, Andersen KK, Luyten GPM, Kiilgaard JF, Jager MJ (2017) The prognostic value of AJCC staging in uveal melanoma is enhanced by adding chromosome 3 and 8q status. Invest Ophthalmol Vis Sci 58:833–842

    PubMed  Google Scholar 

  • Dong X, Qin J, Ma J, Zeng Q, Zhang H, Zhang R, Liu C, Xu C, Zhang S, Huang S, Chen L (2019) BAFF inhibits autophagy promoting cell proliferation and survival by activating Ca(2+)-CaMKII-dependent Akt/mTOR signaling pathway in normal and neoplastic B-lymphoid cells. Cell Signal 53:68–79

    CAS  PubMed  Google Scholar 

  • Dou H, Yan Z, Zhang M, Xu X (2016) APRIL, BCMA and TACI proteins are abnormally expressed in non-small cell lung cancer. Oncol Lett 12:3351–3355

    CAS  PubMed  PubMed Central  Google Scholar 

  • Durante MA, Rodriguez DA, Kurtenbach S, Kuznetsov JN, Sanchez MI, Decatur CL, Snyder H, Feun LG, Livingstone AS, Harbour JW (2020) Single-cell analysis reveals new evolutionary complexity in uveal melanoma. Nature Communications 11:496

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fu L, Lin-Lee YC, Pham LV, Tamayo AT, Yoshimura LC, Ford RJ (2009) BAFF-R promotes cell proliferation and survival through interaction with IKKbeta and NF-kappaB/c-Rel in the nucleus of normal and neoplastic B-lymphoid cells. Blood 113:4627–4636

    CAS  PubMed  PubMed Central  Google Scholar 

  • García-Castro A, Zonca M, Florindo-Pinheiro D, Carvalho-Pinto CE, Cordero A, Gutiérrez del Fernando A, García-Grande A, Mañes S, Hahne M, González-Suárez E, Planelles L (2015) APRIL promotes breast tumor growth and metastasis and is associated with aggressive basal breast cancer. Carcinogenesis 36:574–584

    PubMed  Google Scholar 

  • Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    CAS  PubMed  Google Scholar 

  • Haritoglou I, Wolf A, Maier T, Haritoglou C, Hein R, Schaller UC (2009) Osteopontin and “melanoma inhibitory activity”: comparison of two serological tumor markers in metastatic uveal melanoma patients. Ophthalmologica 223:239–243

    CAS  PubMed  Google Scholar 

  • Kadkol SS, Lin AY, Barak V, Kalickman I, Leach L, Valyi-Nagy K, Majumdar D, Setty S, Maniotis AJ, Folberg R, Pe’Er J (2006) Osteopontin expression and serum levels in metastatic uveal melanoma: a pilot study. Invest Ophthalmol Vis Sci 47:802–806

    PubMed  Google Scholar 

  • Kaliki S, Shields CL, Shields JA (2015) Uveal melanoma: estimating prognosis. Indian J Ophthalmol 63:93–102

    PubMed  PubMed Central  Google Scholar 

  • Keilholz U, Goldin-Lang P, Bechrakis NE, Max N, Letsch A, Schmittel A, Scheibenbogen C, Heufelder K, Eggermont A, Thiel E (2004) Quantitative detection of circulating tumor cells in cutaneous and ocular melanoma and quality assessment by real-time reverse transcriptase-polymerase chain reaction. Clin Cancer Res 10:1605–1612

    CAS  PubMed  Google Scholar 

  • Kern C, Cornuel J-FO, Billard C, Tang R, Rouillard D, Stenou V, Defrance T, Ajchenbaum-Cymbalista F, Simonin P-Y, Feldblum S, Kolb J-P (2004) Involvement of BAFF and APRIL in the resistance to apoptosis of B-CLL through an autocrine pathway. Blood 103:679–688

    CAS  PubMed  Google Scholar 

  • Kluger HM, Hoyt K, Bacchiocchi A, Mayer T, Kirsch J, Kluger Y, Sznol M, Ariyan S, Molinaro A, Halaban R (2011) Plasma markers for identifying patients with metastatic melanoma. Clin Cancer Res 17:2417

    CAS  PubMed  PubMed Central  Google Scholar 

  • Koizumi M, Hiasa Y, Kumagi T, Yamanishi H, Azemoto N, Kobata T, Matsuura B, Abe M, Onji M (2013a) Increased B cell-activating factor promotes tumor invasion and metastasis in human pancreatic cancer. PLoS ONE 8:e71367

    CAS  PubMed  PubMed Central  Google Scholar 

  • Koizumi M, Hiasa Y, Kumagi T, Yamanishi H, Azemoto N, Kobata T, Matsuura B, Abe M, Onji MJPO (2013b) Increased B cell-activating factor promotes tumor invasion and metastasis in human pancreatic cancer. PLoS ONE 8:e71367

    CAS  PubMed  PubMed Central  Google Scholar 

  • Krantz BA, Dave N, Komatsubara KM, Marr BP, Carvajal RD (2017) Uveal melanoma: epidemiology, etiology, and treatment of primary disease. Clin Ophthalmol 11:279–289

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kreuzaler M, Rauch M, Salzer U, Birmelin J, Rizzi M, Grimbacher B, Plebani A, Lougaris V, Quinti I, Thon V, Litzman J, Schlesier M, Warnatz K, Thiel J, Rolink AG, Eibel H (2012) Soluble BAFF levels inversely correlate with peripheral B cell numbers and the expression of BAFF receptors. J Immunol 188:497

    CAS  PubMed  Google Scholar 

  • Krishna Y, Acha-Sagredo A, Sabat-Pośpiech D, Kipling N, Clarke K, Figueiredo CR, Kalirai H, Coupland SE (2020) Transcriptome profiling reveals new insights into the immune microenvironment and upregulation of novel biomarkers in metastatic uveal melanoma. Cancers (Basel) 12:2832

    CAS  Google Scholar 

  • Li H, van der Leun AM, Yofe I, Lubling Y, Gelbard-Solodkin D, van Akkooi ACJ, van den Braber M, Rozeman EA, Haanen JBAG, Blank CU, Horlings HM, David E, Baran Y, Bercovich A, Lifshitz A, Schumacher TN, Tanay A, Amit I (2019) Dysfunctional CD8 T cells form a proliferative, dynamically regulated compartment within human melanoma. Cell 176:775-789.e18

    CAS  PubMed  Google Scholar 

  • Lied GA, Berstad A (2011) Functional and clinical aspects of the B-cell-activating factor (BAFF): a narrative review. Scand J Immunol 73:1–7

    CAS  PubMed  Google Scholar 

  • Liotta LA, Ferrari M, Petricoin E (2003) Clinical proteomics: written in blood. Nature 425:905

    CAS  PubMed  Google Scholar 

  • Liu YM, Li Y, Wei WB, Xu X, Jonas JB (2015) Clinical Characteristics of 582 patients with uveal melanoma in China. PLoS ONE 10:e0144562

    PubMed  PubMed Central  Google Scholar 

  • Long T, Su J, Tang W, Luo Z, Liu S, Liu Z, Zhou H, Qi M, Zeng W, Zhang J, Chen X (2013) A novel interaction between calcium-modulating cyclophilin ligand and Basigin regulates calcium signaling and matrix metalloproteinase activities in human melanoma cells. Cancer Lett 339:93–101

    CAS  PubMed  Google Scholar 

  • Ma ST, Hsieh YT, Wei YH, Liao SL (2020) A 45-year experience of uveal melanoma in Taiwan: verification of American Joint Committee on Cancer staging system and prognostic factors. J Formos Med Assoc. https://doi.org/10.1016/j.jfma.2020.10.016

    Article  PubMed  PubMed Central  Google Scholar 

  • Mackay F, Browning JL (2002) BAFF: a fundamental survival factor for B cells. Nat Rev Immunol 2:465–475

    CAS  PubMed  Google Scholar 

  • Mackay F, Schneider P (2009) Cracking the BAFF code. Nat Rev Immunol 9:491–502

    CAS  PubMed  Google Scholar 

  • Mäkitie R, Summanen P, Tarkkanen A, Kivelä T (2001) Tumor-infiltrating macrophages (cd68+ cells) and prognosis in malignant uveal melanoma. Investig Ophthalmol Vis Sci 42:1414–1421

    Google Scholar 

  • Mao R, Trajtman A, Head B, Rodríguez IA, Sabogal, Cabrera R, Marín D, López L, Rodiño J, Aguilar Y, Herrera M, Díaz, Vélez LA, RuedaKeynan ZVY (2019) Inflammatory cell differentiation and chemotaxis and extracellular tissue repair markers are correlated with pulmonary dysfunction in hiv infected individuals presenting with community-acquired pneumonia. J Interferon Cytokine Res 40:106–115

    PubMed  Google Scholar 

  • McCarthy C, Kalirai H, Lake SL, Dodson A, Damato BE, Coupland SE (2016) Insights into genetic alterations of liver metastases from uveal melanoma. Pigment Cell Melanoma Res 29:60–67

    CAS  PubMed  Google Scholar 

  • Missotten GS, Tang NE, Korse CM, Hurks HM, De Wolff-Rouendaal D, Keunen JE, Jager MJ, Bonfrer JM (2003) Prognostic value of S-100-beta serum concentration in patients with uveal melanoma. Arch Ophthalmol 121:1117–1119

    CAS  PubMed  Google Scholar 

  • Moreaux J, Veyrune JL, de Vos J, Klein B (2009) APRIL is overexpressed in cancer: link with tumor progression. BMC Cancer 9:83

    PubMed  PubMed Central  Google Scholar 

  • Park S, Jang J-W, Moon E-Y (2020) BAFF attenuates oxidative stress-induced cell death by the regulation of mitochondria membrane potential via Syk activation in WiL2-NS B lymphoblasts. Sci Rep 10:11784

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pelekanou V, Notas G, Athanasouli P, Alexakis K, Kiagiadaki F, Peroulis N, Kalyvianaki K, Kampouri E, Polioudaki H, Theodoropoulos P, Tsapis A, Castanas E, Kampa M (2018) BCMA (TNFRSF17) induces APRIL and BAFF mediated breast cancer cell stemness. Front Oncol 8:301

    PubMed  PubMed Central  Google Scholar 

  • Piperno-neumann S, Piulats MJ, Goebeller M, Galloway I, Lugowska I, Becker CJ, Vihinen P, Van Cluster J, Hadjistilianou J, Proença R, Caminal MJ, Rogasik M, Blay J-Y, Kapiteijn E (2019) Uveal melanoma: a European Network to face the many challenges of a rare cancer. Cancers 11:817

    CAS  PubMed Central  Google Scholar 

  • Polak ME, Borthwick NJ, Johnson P, Hungerford JL, Higgins B, di Palma S, Jager MJ, Cree IA (2007) Presence and phenotype of dendritic cells in uveal melanoma. Br J Ophthalmol 91:971–976

    PubMed  PubMed Central  Google Scholar 

  • Prescher G, Bornfeld N, Hirche H, Horsthemke B, Jöckel KH, Becher R (1996) Prognostic implications of monosomy 3 in uveal melanoma. Lancet 347:1222–1225

    CAS  PubMed  Google Scholar 

  • Rahman ZSM, Manser T (2004) B cells expressing Bcl-2 and a signaling-impaired BAFF-specific receptor fail to mature and are deficient in the formation of lymphoid follicles and germinal centers. J Immunol 173:6179

    CAS  PubMed  Google Scholar 

  • Reiniger IW, Schaller UC, Haritoglou C, Hein R, Bosserhoff AK, Kampik A, Mueller AJ (2005) “Melanoma inhibitory activity” (MIA): a promising serological tumour marker in metastatic uveal melanoma. Graefe’s ArchClin Exp Ophthalmol 243:1161–1166

    CAS  Google Scholar 

  • Reiniger IW, Wolf A, Welge-Lüssen U, Mueller AJ, Kampik A, Schaller UC (2007) Osteopontin as a serologic marker for metastatic uveal melanoma: results of a pilot study. Am J Ophthalmol 143:705–707

    CAS  PubMed  Google Scholar 

  • Richert Q, Trajtman A, Arroyave L, Toews J, Becker M, Kasper K, McLaren P, Rueda Z, Keynan Y (2017) Systemic inflammation before and after antiretroviral therapy initiation as a predictor of immune response among HIV-infected individuals in Manitoba. Cytokine 91:74–81

    CAS  PubMed  Google Scholar 

  • Rizzardi AE, Johnson AT, Vogel RI, Pambuccian SE, Henriksen J, Skubitz AP, Metzger GJ, Schmechel SC (2012) Quantitative comparison of immunohistochemical staining measured by digital image analysis versus pathologist visual scoring. Diagn Pathol 7:42–42

    PubMed  PubMed Central  Google Scholar 

  • Robertson AG, Shih J, Yau C, Gibb EA, Oba J, Mungall KL, Hess JM, Uzunangelov V, Walter V, Danilova L, Lichtenberg TM, Kucherlapati M, Kimes PK, Tang M, Penson A, Babur O, Akbani R, Bristow CA, Hoadley KA, Iype L, Chang MT, Abdel-Rahman MH, Akbani R, Ally A, Auman JT, Babur O, Balasundaram M, Balu S, Benz C, Beroukhim R, Birol I, Bodenheimer T, Bowen J, Bowlby R, Bristow CA, Brooks D, Carlsen R, Cebulla CM, Chang MT, Cherniack AD, Chin L, Cho J, Chuah E, Chudamani S, Cibulskis C, Cibulskis K, Cope L, Coupland SE, Danilova L, Defreitas T, Demchok JA, Desjardins L, Dhalla N, Esmaeli B, Felau I, Ferguson ML, Frazer S, Gabriel SB, Gastier-Foster JM, Gehlenborg N, Gerken M, Gershenwald JE, Getz G, Gibb EA, Griewank KG, Grimm EA, Hayes DN, Hegde AM, Heiman DI, Helsel C, Hess JM, Hoadley KA, Hobensack S, Holt RA, Hoyle AP, Hu X, Hutter CM, Jager MJ, Jefferys SR, Jones CD, Jones SJM, Kandoth C, Kasaian K, Kim J, Kimes PK, Kucherlapati M, Kucherlapati R, Lander E, Lawrence MS, Lazar AJ, Lee S, Leraas KM, Lichtenberg TM, Lin P, Liu J, Liu W, Lolla L, Lu Y, Iype L, Ma Y et al (2017) Integrative analysis identifies four molecular and clinical subsets in uveal melanoma. Cancer Cell 32:204-220.e15

    CAS  PubMed  PubMed Central  Google Scholar 

  • Smulski CR, Eibel H (2018) BAFF and BAFF-receptor in B cell selection and survival. Front Immunol 9:2285

    PubMed  PubMed Central  Google Scholar 

  • Suesskind D, Schatz A, Schnichels S, Coupland SE, Lake SL, Wissinger B, Bartz-Schmidt KU, Henke-Fahle S (2012) GDF-15: a novel serum marker for metastases in uveal melanoma patients. Graefes Arch Clin Exp Ophthalmol 250:887–895

    CAS  PubMed  Google Scholar 

  • Triozzi PL, Schoenfield L, Plesec T, Saunthararajah Y, Tubbs RR, Singh AD (2019) Molecular profiling of primary uveal melanomas with tumor-infiltrating lymphocytes. OncoImmunology 8:e947169

    PubMed  Google Scholar 

  • Tura A, Lüke J, Merz H, Reinsberg M, Lüke M, Jager MJ, Grisanti S (2014) Identification of circulating melanoma cells in uveal melanoma patients by dual-marker immunoenrichment. Invest Ophthalmol Vis Sci 55:4395–4404

    PubMed  Google Scholar 

  • Tura A, Merz H, Reinsberg M, Lüke M, Jager MJ, Grisanti S, Lüke J (2016) Analysis of monosomy-3 in immunomagnetically isolated circulating melanoma cells in uveal melanoma patients. Pigment Cell Melanoma Res 29:583–589

    CAS  PubMed  Google Scholar 

  • Youden WJ (1950) Index for rating diagnostic tests. Cancer 3:32–35

    CAS  PubMed  Google Scholar 

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Funding

Zenan Lin was supported by the China Scholarship Council (CSC) Program (Grant No.: 201708080023).

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  1. Center for Ophthalmology, University Eye Hospital, University of Tübingen, Elfriede-Aulhorn-Strasse 7, 72076, Tübingen, Germany

    Zenan Lin & Daniela Süsskind

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  1. Zenan Lin
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Contributions

We would like to thank UH, CR, HE, and M Wild for their excellent assistance of the experimental work. We also would like to thank Dr. Y-SF of the Institute for Clinical Epidemiology and Applied Biometry, University Hospital of Tübingen for the statistical consulting. DS conceived and supervised the whole project. ZL acquired and analysed the experimental data. ZL drafted the manuscript. DS revised the manuscript. The authors declared no conflict of interest.

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Correspondence to Zenan Lin.

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Lin, Z., Süsskind, D. Exploring the role of BAFF as biomarker in the detection of uveal melanoma metastases. J Cancer Res Clin Oncol 147, 1389–1405 (2021). https://doi.org/10.1007/s00432-021-03555-0

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