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.
Highlights
The latest epidemiological statistics position malignant melanoma (MM) as the third and most deadly type of skin cancer, while basal cell carcinoma is by far the most common type of skin cancer
The initial step of a Selected Reaction Monitoring (SRM) assay development usually relates to apply an in silico step, where a selection of suitable peptides from the proteins are made, followed by BLAST searching in protein database, where identified peptides from the proteins can verify the utility of target peptides identified as candidates
We have developed and applied a SRM assay for quantification of alpha-synuclein in MM tissue lysate using a stable isotope dilution strategy
Summary
The latest epidemiological statistics position malignant melanoma (MM) as the third and most deadly type of skin cancer, while basal cell carcinoma is by far the most common type of skin cancer. Matsuo et al have shown that determination of alpha-synuclein protein expression could be useful for the diagnosis of metastatic melanoma, it cannot be used to distinguish between malignant and benign melanocytic skin lesions since melanosomes express alphasynuclein [7]. There has been growing evidence in the literature for mutual mechanisms between cancer and CNS disorders [11], and especially on shared risk and overlapping disease mechanisms in the development of PD and MM [12,13,14,15]. These findings suggested a link between MM and PD. Current hypotheses focus towards alpha-synuclein oligomers being the more toxic species [4,17,18]
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