Protein signatures correspond to survival outcomes of AJCC stage III melanoma patients |
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| Authors: | Swetlana Mactier Kimberley L. Kaufman Penghao Wang Ben Crossett Gulietta M. Pupo Philippa L. Kohnke John F. Thompson Richard A. Scolyer Jean Y. Yang Graham J. Mann Richard I. Christopherson |
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| Affiliation: | 1. School of Molecular Bioscience, University of Sydney, , Sydney, NSW, Australia;2. School of Mathematics and Statistics, University of Sydney, , Sydney, NSW, Australia;3. Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, , Westmead, NSW, Australia;4. Melanoma Institute Australia, , Crows Nest, NSW, Australia;5. Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, , Camperdown, NSW, Australia;6. Discipline of Surgery, Sydney Medical School, The University of Sydney, , Sydney, NSW, Australia;7. Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, , Camperdown, NSW, Australia;8. Discipline of Pathology, Sydney Medical School, The University of Sydney, , Sydney, NSW, Australia |
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| Abstract: | Outcomes for melanoma patients with stage III disease differ widely even within the same subcategory. Molecular signatures that more accurately predict prognosis are needed to stratify patients according to risk. Proteomic analyses were used to identify differentially abundant proteins in extracts of surgically excised samples from patients with stage IIIc melanoma lymph node metastases. Analysis of samples from patients with poor (n = 14, <1 yr) and good (n = 19, >4 yr) survival outcomes identified 84 proteins that were differentially abundant between prognostic groups. Subsequent selected reaction monitoring analysis verified 21 proteins as potential biomarkers for survival. Poor prognosis patients are characterized by increased levels of proteins involved in protein metabolism, nucleic acid metabolism, angiogenesis, deregulation of cellular energetics and methylation processes, and decreased levels of proteins involved in apoptosis and immune response. These proteins are able to classify stage IIIc patients into prognostic subgroups (P < 0.02). This is the first report of potential prognostic markers from stage III melanoma using proteomic analyses. Validation of these protein markers in larger patient cohorts should define protein signatures that enable better stratification of stage III melanoma patients. |
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| Keywords: | melanoma lymph node metastasis prognosis iTRAQ 2DLC‐MS/MS DIGE protein markers SRM |
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