TY - JOUR
T1 - Analysis of Alpha-Synuclein in Malignant Melanoma - Development of a SRM Quantification Assay.
AU - Welinder, Charlotte
AU - Jönsson, Göran B
AU - Ingvar, Christian
AU - Lundgren, Lotta
AU - Baldetorp, Bo
AU - Olsson, Håkan
AU - Breslin, Thomas
AU - Rezeli, Melinda
AU - Jansson, Bo
AU - Fehniger, Thomas E
AU - Laurell, Thomas
AU - Wieslander, Elisabet
AU - Pawlowski, Krzysztof
AU - Marko-Varga, György
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
U2 - 10.1371/journal.pone.0110804
DO - 10.1371/journal.pone.0110804
M3 - Article
C2 - 25333933
SN - 1932-6203
VL - 9
JO - PLoS ONE
JF - PLoS ONE
IS - 10
M1 - e110804
ER -
