title: MALDI imaging mass spectrometry in ovarian cancer for tracking, identifying, and validating biomarkers.
abstract: BACKGROUND
  Among biomarkers, cancer-antigen 125 (CA-125) is the most studied. We propose an analytical tool to track ovarian carcinoma biomarkers, that is, the MALDI mass spectrometry imaging.
  
  
  METHODS
  Ovarian carcinomas and benign ovaries were directly analyzed by MALDI-TOF-MS. After automatic profiling and mass spectrometry imaging analyses, hierarchical clustering based on principal component analysis in nonsupervised mode was carried out. On the same samples, preparations were performed to investigate peptides, then proteins, followed by high mass proteins, in an automatic profiling to specific signatures for diagnosis. Using tissue bottom-up strategy on tissue digestion, and mass spectrometry imaging after by shotgun sequencing by nalano-LC-IT-MS in MS/MS mode from washing samples from on tissue digested peptides, several biomarkers were found.
  
  
  RESULTS
  A list of specific biomarkers from the ovarian carcinoma regions was obtained and classified as proteins associated with cell proliferation, involved in immune response modulation, signaling to the cytoskeleton, and tumor progression. These specific biomarkers were then validated by immunocytochemistry using Tag-mass technology, cell biology, Western blot, and by PCR (using SKOV-3 ovarian epithelial cancer cells). A link between the immune regulation (innate immunity, tolerance) and virus cause is also discussed.
  
  
  CONCLUSIONS
  From the biomarkers identified, proteins involved in immune response modulation and cell proliferation have been pointed out in this study. Two new markers have been identified using such a strategy, that is, fragment C-terminal of the PSME1 (Reg-Alpha) and mucin-9.
authors.affiliation: Université Nord de France, CNRS, MALDI Imaging Team, Laboratoire de Neuroimmunologie et Neurochimie Evolutives, Université Lille 1, Lille, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: El Ayed
authors.forename: David
authors.initials: D
authors.lastname: Bonnel
authors.forename: Remi
authors.initials: R
authors.lastname: Longuespée
authors.forename: Céline
authors.initials: C
authors.lastname: Castelier
authors.forename: Julien
authors.initials: J
authors.lastname: Franck
authors.forename: Daniele
authors.initials: D
authors.lastname: Vergara
authors.forename: Annie
authors.initials: A
authors.lastname: Desmons
authors.forename: Aurélie
authors.initials: A
authors.lastname: Tasiemski
authors.forename: Abderraouf
authors.initials: A
authors.lastname: Kenani
authors.forename: Denis
authors.initials: D
authors.lastname: Vinatier
authors.forename: Robert
authors.initials: R
authors.lastname: Day
authors.forename: Isabelle
authors.initials: I
authors.lastname: Fournier
authors.forename: Michel
authors.initials: M
authors.lastname: Salzet
mesh_terms: D002288:Adenocarcinoma, Mucinous; D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D036103:Nanotechnology; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D025341:Principal Component Analysis; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins