title: Protein signatures correspond to survival outcomes of AJCC stage III melanoma patients.
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.
authors.affiliation: School of Molecular Bioscience, University of Sydney, Sydney, NSW, Australia.
authors.forename: Swetlana
authors.initials: S
authors.lastname: Mactier
authors.forename: Kimberley L
authors.initials: KL
authors.lastname: Kaufman
authors.forename: Penghao
authors.initials: P
authors.lastname: Wang
authors.forename: Ben
authors.initials: B
authors.lastname: Crossett
authors.forename: Gulietta M
authors.initials: GM
authors.lastname: Pupo
authors.forename: Philippa L
authors.initials: PL
authors.lastname: Kohnke
authors.forename: John F
authors.initials: JF
authors.lastname: Thompson
authors.forename: Richard A
authors.initials: RA
authors.lastname: Scolyer
authors.forename: Jean Y
authors.initials: JY
authors.lastname: Yang
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Mann
authors.forename: Richard I
authors.initials: RI
authors.lastname: Christopherson
mesh_terms: D016000:Cluster Analysis; D015180:Electrophoresis, Gel, Two-Dimensional; D053263:Gene Regulatory Networks; D006801:Humans; D007553:Isotope Labeling; D053208:Kaplan-Meier Estimate; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology*; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D015203:Reproducibility of Results; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology*; D053719:Tandem Mass Spectrometry
chemical_list: D009363:Neoplasm Proteins
keywords: DIGE; SRM; iTRAQ 2DLC-MS/MS; lymph node metastasis; melanoma; prognosis; protein markers