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. 2014 Dec 1;9(12):e112025.
doi: 10.1371/journal.pone.0112025. eCollection 2014.

Proteomic profile and in silico analysis in metastatic melanoma with and without BRAF mutation

Vito Michele Garrisi  1 , Sabino Strippoli  1 , Simona De Summa  1 , Rosamaria Pinto  1 , Antonella Perrone  1 , Gabriella Guida  2 , Amalia Azzariti  1 , Michele Guida  1 , Stefania Tommasi
Affiliations

Proteomic profile and in silico analysis in metastatic melanoma with and without BRAF mutation

Vito Michele Garrisi et al. PLoS One. .

Erratum in

Abstract

Introduction: Selective inhibitors of BRAF, vemurafenib and dabrafenib are the standard of care for metastatic melanoma patients with BRAF V600, while chemotherapy continued to be widely used in BRAF wild type patients.

Materials and methods: In order to discover novel candidate biomarkers predictive to treatment, serum of 39 metastatic melanoma vemurafenib (n = 19) or chemotherapy (n = 20) treated patients at baseline, at disease control and at progression, were analyzed using SELDI-TOF technology. In silico analysis was used to identify more significant peaks.

Results: In patients with different BRAF status, we found 5 peptides significantly deregulated, with the down-regulation of the m/z 9176 peak strongly associated with BRAF mutation. At baseline as predictive biomarkers we identified 2 peptides - m/z 6411, 4075 - as significantly up-regulated in responders to chemotherapy and 4 peaks - m/z 5900, 12544, 49124 and 11724 - significantly up-regulated in longer vs shorter responders to vemurafenib. After response, 3 peptides (m/z 4658, 18639, and 9307) resulted significantly down regulated while 3 peptides m/z 9292, 7765 and 9176 appeared up-regulated respectively in chemotherapy and vemurafenib responder patients. In vemurafenib treated patients, 16 peaks appeared deregulated at progression compared to baseline time. In silico analysis identified proteins involved in invasiveness (SLAIN1) and resistance (ABCC12) as well as in the pathway of detoxification (NQO1) and apoptosis (RBM10, TOX3, MTEFD1, TSPO2). Proteins associated with the modulation of neuronal plasticity (RIN1) and regulatory activity factors of gene transcription (KLF17, ZBTB44) were also highlighted.

Conclusion: Our exploratory study highlighted some factors that deserve to be further investigated in order to provide a framework for improving melanoma treatment management through the development of biomarkers which could act as the strongest surrogates of the key biological events in stage IV melanoma.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Representative example of fractionated serum protein profiles of two temozolomide/fotemustine treated patients (from responder and a non-responder patients).
Figure 2
Figure 2. Progression free survival in TMZ/FM treated patients with respect to m/z 6411 and 4075 overexpression.
The median value of expression has been considered as cutoff to discriminate peak overexpression. p = 0.024. —: patients with basal level of the 2 peaks; ---: patients with overexpression of both peaks.
Figure 3
Figure 3. Kaplan-Meyer analysis which considered contemporary up-regulation of all 4 peaks (m/z 5900, 12544, 49124, 11724) with respect to progression free survival in patients treated with vemurafenib.
p = 0.011. —: patients with basal level of the 4 peaks; ---: patients with overexpression of all 4 peaks.
See this image and copyright information in PMC

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