title: A novel biomarker harvesting nanotechnology identifies Bak as a candidate melanoma biomarker in serum.
abstract: BACKGROUND
  Melanoma represents only 4% of all skin cancers, but nearly 80% of skin cancer deaths. This manuscript applies several new measurement technologies with the purpose of elucidating molecular signatures of melanoma aggressiveness.
  
  
  OBJECTIVE
  We sought to determine whether low-abundant serum proteins related to apoptotic pathways could be measured and correlated with defined melanoma subtypes. Hydrogel core shell nanoparticles, a new technology capable of selectively entrapping low molecular weight proteins and protecting them from enzymatic degradation, were used to capture candidate serum biomarkers. Biomarker levels were correlated with confocal microscopy, thereby representing a combination of new technologies for in vivo histologic documentation.
  
  
  RESULTS
  Among a panel of analyzed serum proteins, Bak was differentially expressed between nevi and melanomas. Melanomas with higher Bak serum levels exhibited more pronounced junctional activity on confocal imaging, whereas lesions with 'sparse' dermal nests had weak Bak expression.
  
  
  CONCLUSIONS
  Our study links serum proteome analysis with confocal microscopic clinical in vivo histologic classification of melanomas. Bak has not been previously measured in serum. Bak differential expression among melanoma subtypes confirms the importance of the apoptotic pathway as a contributor to melanoma aggressiveness.
authors.affiliation: Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA. caterina.longo@unimore.it
authors.forename: Caterina
authors.initials: C
authors.lastname: Longo
authors.forename: Guido
authors.initials: G
authors.lastname: Gambara
authors.forename: Virginia
authors.initials: V
authors.lastname: Espina
authors.forename: Alessandra
authors.initials: A
authors.lastname: Luchini
authors.forename: Barney
authors.initials: B
authors.lastname: Bishop
authors.forename: Alexis S
authors.initials: AS
authors.lastname: Patanarut
authors.forename: Emanuel F
authors.initials: EF
authors.lastname: Petricoin
authors.forename: Francesca
authors.initials: F
authors.lastname: Beretti
authors.forename: Barbara
authors.initials: B
authors.lastname: Ferrari
authors.forename: Enrico
authors.initials: E
authors.lastname: Garaci
authors.forename: Anto
authors.initials: A
authors.lastname: De Pol
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pellacani
authors.forename: Lance A
authors.initials: LA
authors.lastname: Liotta
mesh_terms: D000328:Adult; D000077214:Becaplermin; D014408:Biomarkers, Tumor / Q000097:blood*; D006801:Humans; D008545:Melanoma / Q000097:blood* / Q000175:diagnosis / Q000473:pathology / Q000556:secondary; D018613:Microscopy, Confocal; D008875:Middle Aged; D053758:Nanoparticles; D036103:Nanotechnology; D009508:Nevus, Pigmented / Q000097:blood / Q000175:diagnosis; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000097:blood; D020574:Proto-Oncogene Proteins c-sis; D012878:Skin Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000097:blood*
chemical_list: C494772:BAK1 protein, human; D014408:Biomarkers, Tumor; D010982:Platelet-Derived Growth Factor; D019253:Proto-Oncogene Proteins c-bcl-2; D020574:Proto-Oncogene Proteins c-sis; D050998:bcl-2 Homologous Antagonist-Killer Protein; D000077214:Becaplermin