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Serum Proteomic Fingerprinting Discriminates Between Clinical Stages and Predicts Disease Progression in Melanoma Patients

From the Interdisciplinary Biomedical Research Centre, School of Science, Nottingham Trent University, Clifton Lane, Clifton; School of Mathematical Sciences, University of Nottingham, University Park, Nottingham; Department of Animal Physiology, School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough, United Kingdom; Skin Cancer Unit, German Cancer Research Center, Heidelberg; Department of Dermatology, University Hospital, Mannheim, Germany

Address reprint requests to Professor Robert Rees, Interdisciplinary Biomedical Research Centre, School of Science, Nottingham Trent University, Clifton Lane, Clifton, Nottingham NG11 8NS, United Kingdom; e-mail: robert.rees{at}ntu.ac.uk

PURPOSE: Currently known serum biomarkers do not predict clinical outcome in melanoma. S100-ß is widely established as a reliable prognostic indicator in patients with advanced metastatic disease but is of limited predictive value in tumor-free patients. This study was aimed to determine whether molecular profiling of the serum proteome could discriminate between early- and late-stage melanoma and predict disease progression.

PATIENTS AND METHODS: Two hundred five serum samples from 101 early-stage (American Joint Committee on Cancer [AJCC] stage I) and 104 advanced stage (AJCC stage IV) melanoma patients were analyzed by matrix-assisted laser desorption/ionisation (MALDI) time-of-flight (ToF; MALDI-ToF) mass spectrometry utilizing protein chip technology and artificial neural networks (ANN). Serum samples from 55 additional patients after complete dissection of regional lymph node metastases (AJCC stage III), with 28 of 55 patients relapsing within the first year of follow-up, were analyzed in an attempt to predict disease recurrence. Serum S100-ß was measured using a sandwich immunoluminometric assay.

RESULTS: Analysis of 205 stage I/IV serum samples, utilizing a training set of 94 of 205 and a test set of 15 of 205 samples for 32 different ANN models, revealed correct stage assignment in 84 (88%) of 96 of a blind set of 96 of 205 serum samples. Forty-four (80%) of 55 stage III serum samples could be correctly assigned as progressors or nonprogressors using random sample cross-validation statistical methodologies. Twenty-three (82%) of 28 stage III progressors were correctly identified by MALDI-ToF combined with ANN, whereas only six (21%) of 28 could be detected by S100-ß.

CONCLUSION: Validation of these findings may enable proteomic profiling to become a valuable tool for identifying high-risk melanoma patients eligible for adjuvant therapeutic interventions.

Supported by the European Union grant QLG1-CT-2002-00668 (OISTER) and the John and Lucille van Geest Foundation.

All authors have contributed equally to this manuscript.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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