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Affinity Proteomics Exploration of Melanoma Identifies Proteins in Serum with Associations to T-Stage and Recurrence
KTH Royal Inst Technol, Affin Prote, SciLifeLab, S-17165 Solna, Sweden..
KTH Royal Inst Technol, Affin Prote, SciLifeLab, S-17165 Solna, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab. (Forskargrupp Tobias Sjöblom)
KTH Royal Inst Technol, Affin Prote, SciLifeLab, S-17165 Solna, Sweden..
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2017 (English)In: Translational Oncology, ISSN 1944-7124, E-ISSN 1936-5233, Vol. 10, no 3, 385-395 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Blood-based proteomic profiling may aid and expand our understanding of diseases and their different phenotypes. The aim of the presented study was to profile serum samples from patients with malignant melanoma using affinity proteomic assays to describe proteins in the blood stream that are associated to stage or recurrence of melanoma. MATERIAL AND METHODS: Multiplexed protein analysis was conducted using antibody suspension bead arrays. A total of 232 antibodies against 132 proteins were selected from (i) a screening with 4595 antibodies and 32 serum samples from melanoma patients and controls, (ii) antibodies used for immunohistochemistry, (iii) protein targets previously related with melanoma. The analysis was performed with 149 serum samples from patients with malignant melanoma. Antibody selectivity was then assessed by Western blot, immunocapture mass spectrometry, and epitope mapping. Lastly, indicative antibodies were applied for IHC analysis of melanoma tissues. RESULTS: Serum levels of regucalcin (RGN) and syntaxin 7 (STX7) were found to be lower in patients with both recurring tumors and a high Breslow's thickness (T-stage 3/4) compared to low thickness (T-stage 1/2) without disease recurrence. Serum levels of methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) were instead elevated in sera of T3/4 patients with recurrence. The analysis of tissue sections with S100A6 and MTHFD1L showed positive staining in a majority of patients with melanoma, and S100A6 was significantly associated to T-stage. CONCLUSIONS: Our findings provide a starting point to further study RGN, STX7, MTHFD1L and S100A6 in serum to elucidate their involvement in melanoma progression and to assess a possible contribution to support clinical indications.

Place, publisher, year, edition, pages
2017. Vol. 10, no 3, 385-395 p.
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Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-333614DOI: 10.1016/j.tranon.2017.03.002ISI: 000407707600012PubMedID: 28433799OAI: oai:DiVA.org:uu-333614DiVA: diva2:1157761
Funder
Knut and Alice Wallenberg FoundationScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
Available from: 2017-11-16 Created: 2017-11-16 Last updated: 2017-11-16Bibliographically approved

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Edqvist, Per-Henrik DBergqvist, MichaelPonten, Fredrik

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Experimental and Clinical OncologyScience for Life Laboratory, SciLifeLabCentre for Research and Development, GävleborgClinical and experimental pathology
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