title: Plasma Proteomic Profiling in Hereditary Breast Cancer Reveals a BRCA1-Specific Signature: Diagnostic and Functional Implications.
abstract: BACKGROUND
  Breast cancer (BC) is a leading cause of death among women. Among the major risk factors, an important role is played by familial history of BC. Germ-line mutations in BRCA1/2 genes account for most of the hereditary breast and/or ovarian cancers. Gene expression profiling studies have disclosed specific molecular signatures for BRCA1/2-related breast tumors as compared to sporadic cases, which might help diagnosis and clinical follow-up. Even though, a clear hallmark of BRCA1/2-positive BC is still lacking. Many diseases are correlated with quantitative changes of proteins in body fluids. Plasma potentially carries important information whose knowledge could help to improve early disease detection, prognosis, and response to therapeutic treatments. The aim of this study was to develop a comprehensive approach finalized to improve the recovery of specific biomarkers from plasma samples of subjects affected by hereditary BC.
  
  
  METHODS
  To perform this analysis, we used samples from patients belonging to highly homogeneous population previously reported. Depletion of high abundant plasma proteins, 2D gel analysis, liquid chromatography-tandem mass spectrometry (LC-MS/MS) and bioinformatics analysis were used into an integrated approach to investigate tumor-specific changes in the plasma proteome of BC patients and healthy family members sharing the same BRCA1 gene founder mutation (5083del19), previously reported by our group, with the aim to identify specific signatures.
  
  
  RESULTS
  The comparative analysis of the experimental results led to the identification of gelsolin as the most promising biomarker.
  
  
  CONCLUSIONS
  Further analyses, performed using a panel of breast cancer cell lines, allowed us to further elucidate the signaling network that might modulate the expression of gelsolin in breast cancer.
authors.affiliation: Dpt. of Experimental and Clinical Medicine, Magna Græcia University of Catanzaro, Salvatore Venuta University Campus, Catanzaro, Italy.
authors.forename: Domenica
authors.initials: D
authors.lastname: Scumaci
authors.affiliation: Dpt. of Experimental and Clinical Medicine, Magna Græcia University of Catanzaro, Salvatore Venuta University Campus, Catanzaro, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Tammè
authors.affiliation: Dpt. of Experimental and Clinical Medicine, Magna Græcia University of Catanzaro, Salvatore Venuta University Campus, Catanzaro, Italy.
authors.forename: Claudia Vincenza
authors.initials: CV
authors.lastname: Fiumara
authors.affiliation: Dpt. of Experimental and Clinical Medicine, Magna Græcia University of Catanzaro, Salvatore Venuta University Campus, Catanzaro, Italy.
authors.forename: Giusi
authors.initials: G
authors.lastname: Pappaianni
authors.affiliation: Dpt. of Experimental and Clinical Medicine, Magna Græcia University of Catanzaro, Salvatore Venuta University Campus, Catanzaro, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Concolino
authors.affiliation: Dpt. of Experimental and Clinical Medicine, Magna Græcia University of Catanzaro, Salvatore Venuta University Campus, Catanzaro, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Leone
authors.affiliation: Dpt. of Experimental and Clinical Medicine, Magna Græcia University of Catanzaro, Salvatore Venuta University Campus, Catanzaro, Italy.
authors.forename: Maria Concetta
authors.initials: MC
authors.lastname: Faniello
authors.affiliation: Dpt. of Experimental and Clinical Medicine, Magna Græcia University of Catanzaro, Salvatore Venuta University Campus, Catanzaro, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Quaresima
authors.affiliation: Medical Oncology, S. Salvatore Hospital, University of L'Aquila, L'Aquila, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Ricevuto
authors.affiliation: Dpt. of Experimental and Clinical Medicine, Magna Græcia University of Catanzaro, Salvatore Venuta University Campus, Catanzaro, Italy.
authors.forename: Francesco Saverio
authors.initials: FS
authors.lastname: Costanzo
authors.affiliation: Dpt. of Experimental and Clinical Medicine, Magna Græcia University of Catanzaro, Salvatore Venuta University Campus, Catanzaro, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cuda
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics*; D005260:Female; D006801:Humans; D009154:Mutation; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D020543:Proteome; D012333:RNA, Messenger