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Proteomic analysis of the uveal melanoma ( UM ) secretome reveals novel insights and potential biomarkers
Author(s) -
Angi M.,
Kalirai H.,
Coupland S.
Publication year - 2015
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2015.0621
Subject(s) - proteomics , secretory protein , metastasis , cancer , disease , biology , biomarker , pathway analysis , cancer research , downregulation and upregulation , medicine , melanoma , pathology , bioinformatics , secretion , gene , gene expression , genetics
Purpose UM is the most common primary intraocular tumour in adults. Despite successful ocular treatment, 50% of patients develop fatal metastatic spread, usually involving the liver. UM patients are stratified into high risk ( HR ) or low risk ( LR ) metastatic groups, according to clinical, histopathological and genetic features of their tumours. Blood biomarkers are urgently needed to detect the early development of metastatic disease. The aims of this work were to increase our understanding of UM metastasis processes, and to identify secreted biomarkers of UM metastatic disease. Methods Comparative analysis of the secretome from short‐term cultures of HR and LR UM patient samples was performed by nano LC ‐ MS / MS ‐based label‐free quantitative proteomics. Normal (N) controls included the secretome of cultured normal choroidal melanocytes. Secreted proteins were predicted based on their sequences. Bioinformatic analyses were performed using Partek and Ingenuity Pathway Analysis software. Results Eighteen UM (4 LR ; 14 HR ) and 5N cultures were established and their secretomes analysed. 1917 proteins were identified, and 1857 quantified in all subgroups. 627/1857 (34%) were classically and non‐classically secreted, and 554/1857 (30%) represented exosomal proteins. 947 proteins were differentially expressed between UM and N; pathway analysis demonstrated upregulation of proteins involved in mTOR signalling amongst others. An 18‐protein signature that discriminated between HR and LR UM s was identified. Conclusions Our comparative study of the secretome of N versus UM has identified cancer‐associated proteins linked to cell proliferation and cancer progression. Moreover, a UM secretome signature of metastatic risk was identified. Further studies on the exosomal fraction are also being performed.