title: Analysis of alpha-synuclein in malignant melanoma - development of a SRM quantification assay.
abstract: Globally, malignant melanoma shows a steady increase in the incidence among cancer diseases. Malignant melanoma represents a cancer type where currently no biomarker or diagnostics is available to identify disease stage, progression of disease or personalized medicine treatment. The aim of this study was to assess the tissue expression of alpha-synuclein, a protein implicated in several disease processes, in metastatic tissues from malignant melanoma patients. A targeted Selected Reaction Monitoring (SRM) assay was developed and utilized together with stable isotope labeling for the relative quantification of two target peptides of alpha-synuclein. Analysis of alpha-synuclein protein was then performed in ten metastatic tissue samples from the Lund Melanoma Biobank. The calibration curve using peak area ratio (heavy/light) versus concentration ratios showed linear regression over three orders of magnitude, for both of the selected target peptide sequences. In support of the measurements of specific protein expression levels, we also observed significant correlation between the protein and mRNA levels of alpha-synuclein in these tissues. Investigating levels of tissue alpha-synuclein may add novel aspect to biomarker development in melanoma, help to understand disease mechanisms and ultimately contribute to discriminate melanoma patients with different prognosis.
authors.affiliation: Division of Oncology and Pathology, Clinical Sciences, Lund University, Lund, Sweden; Centre of Excellence in Biological and Medical Mass Spectrometry, Lund University, Lund, Sweden.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Welinder
authors.affiliation: Division of Oncology and Pathology, Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Göran B
authors.initials: GB
authors.lastname: Jönsson
authors.affiliation: Skåne University Hospital, Lund, Sweden; Dept. of Surgery, Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Ingvar
authors.affiliation: Division of Oncology and Pathology, Clinical Sciences, Lund University, Lund, Sweden; Skåne University Hospital, Lund, Sweden.
authors.forename: Lotta
authors.initials: L
authors.lastname: Lundgren
authors.affiliation: Division of Oncology and Pathology, Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Baldetorp
authors.affiliation: Division of Oncology and Pathology, Clinical Sciences, Lund University, Lund, Sweden; Skåne University Hospital, Lund, Sweden; Dept. of Cancer Epidemiology, Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Håkan
authors.initials: H
authors.lastname: Olsson
authors.affiliation: Division of Oncology and Pathology, Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Breslin
authors.affiliation: Clinical Protein Science & Imaging, Biomedical Center, Biomedical Engineering, Lund University, Lund, Sweden.
authors.forename: Melinda
authors.initials: M
authors.lastname: Rezeli
authors.affiliation: Division of Oncology and Pathology, Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Jansson
authors.affiliation: Division of Oncology and Pathology, Clinical Sciences, Lund University, Lund, Sweden; Centre of Excellence in Biological and Medical Mass Spectrometry, Lund University, Lund, Sweden.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Fehniger
authors.affiliation: Centre of Excellence in Biological and Medical Mass Spectrometry, Lund University, Lund, Sweden; Clinical Protein Science & Imaging, Biomedical Center, Biomedical Engineering, Lund University, Lund, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Laurell
authors.affiliation: Division of Oncology and Pathology, Clinical Sciences, Lund University, Lund, Sweden.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Wieslander
authors.affiliation: Division of Oncology and Pathology, Clinical Sciences, Lund University, Lund, Sweden; Dept. of Experimental Design and Bioinformatics, Faculty of Agriculture and Biology, Warsaw University of Life Sciences, Warszawa, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Pawlowski
authors.affiliation: Centre of Excellence in Biological and Medical Mass Spectrometry, Lund University, Lund, Sweden; Clinical Protein Science & Imaging, Biomedical Center, Biomedical Engineering, Lund University, Lund, Sweden; First Department of Surgery, Tokyo Medical University, Tokyo, Japan.
authors.forename: György
authors.initials: G
authors.lastname: Marko-Varga
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009928:Organ Specificity; D011379:Prognosis; D040901:Proteomics; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D051844:alpha-Synuclein / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D051844:alpha-Synuclein