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. 2009 Sep;135(9):1257-64.
doi: 10.1007/s00432-009-0567-7. Epub 2009 Mar 14.

Highly sensitive detection of melanoma based on serum proteomic profiling

Julie Caron  1 , Alain Mangé, Bernard Guillot, Jérôme Solassol
Affiliations

Highly sensitive detection of melanoma based on serum proteomic profiling

Julie Caron et al. J Cancer Res Clin Oncol. 2009 Sep.

Abstract

Purpose: There is no available tumor marker that can detect primary melanoma. Proteomics analysis has been proposed as a novel tool that would lead to the discovery of potential new tumor markers.

Methods: We developed a serum proteomic fingerprinting approach coupled with a classification method to determine whether proteomic profiling could discriminate between melanoma and healthy volunteers. A total of 108 serum samples from 30 early-stage [American Joint Committee on Cancer (AJCC) stage I or II] and 30 advanced-stage (AJCC stage III or IV) melanoma patients and 48 healthy volunteers were analyzed by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) utilizing protein chip technology and artificial neural networks.

Results: In a first step, a multiprotein classifier was built using a training set of 30 pathologically confirmed melanoma and 24 healthy volunteer serum samples, resulting in good classification accuracy for correct diagnosis and stage classification assignment. Subsequently, our multiprotein classifier was tested in an independent validation set of 30 melanoma and 24 non-cancer serum samples patients, maintained in a good diagnostic accuracy of 98.1% (sensitivity 96.7%, specificity 100%), and 100% stage I/II classification assignment.

Conclusions: Although results remain to be confirmed in larger collective patient cohorts, we could demonstrate the usefulness of proteomic profiling as a sensitive and specific assay to detect melanoma, including non-metastatic melanoma, from the serum.

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Figures

Fig. 1
Fig. 1
Representative SELDI-TOF spectra obtained from non-cancer and melanoma serum samples. a Overlay of protein mass spectra. Protein mass spectra obtained from sera of patients with melanoma (red) and non-cancer individuals (blue) are superimposed. Differential variations in intensity indicate potential markers. b Representative spectra from three patients with non-cancer (upper panel) and three patients with melanoma (lower panel); the depicted peaks were identified by statistical analysis as optimally discriminatory. Frames indicate the positions of two peaks at 8,117 and 8,586 Da, respectively, overexpressed in fraction 1 of melanoma patients (right panel) and one peak at 28,053 Da underexpressed in fraction 3 of melanoma patients
Fig. 2
Fig. 2
Heat cluster map and principle component analysis (PCA) of melanoma and normal samples. All protein peaks in the 2.5–80 kDa mass range were pooled to generate a heat cluster map (a) and PCA diagram (b). The PCA diagram illustrates the segregated samples based on normal (N) and melanoma (M) samples
See this image and copyright information in PMC

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