title: Proteomic profile and in silico analysis in metastatic melanoma with and without BRAF mutation.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: National Cancer Research Centre, Istituto Tumori "Giovanni Paolo II", Bari, Italy.
authors.forename: Vito Michele
authors.initials: VM
authors.lastname: Garrisi
authors.affiliation: National Cancer Research Centre, Istituto Tumori "Giovanni Paolo II", Bari, Italy.
authors.forename: Sabino
authors.initials: S
authors.lastname: Strippoli
authors.affiliation: National Cancer Research Centre, Istituto Tumori "Giovanni Paolo II", Bari, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: De Summa
authors.affiliation: National Cancer Research Centre, Istituto Tumori "Giovanni Paolo II", Bari, Italy.
authors.forename: Rosamaria
authors.initials: R
authors.lastname: Pinto
authors.affiliation: National Cancer Research Centre, Istituto Tumori "Giovanni Paolo II", Bari, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Perrone
authors.affiliation: Dept. of Basic Medical Sciences, Faculty of Medicine and Surgery, School of Medicine, University of Bari, Bari, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Guida
authors.affiliation: National Cancer Research Centre, Istituto Tumori "Giovanni Paolo II", Bari, Italy.
authors.forename: Amalia
authors.initials: A
authors.lastname: Azzariti
authors.affiliation: National Cancer Research Centre, Istituto Tumori "Giovanni Paolo II", Bari, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Guida
authors.forename: Stefania
authors.initials: S
authors.lastname: Tommasi
authors.affiliation: National Cancer Research Centre, Istituto Tumori "Giovanni Paolo II", Bari, Italy.
authors.forename: Tommasi
authors.initials: T
authors.lastname: Stefania
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003198:Computer Simulation; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D040901:Proteomics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D000077484:Vemurafenib
chemical_list: D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; D048493:Proto-Oncogene Proteins B-raf