title: Proteomic identification of fucosylated haptoglobin alpha isoforms in ascitic fluids and its localization in ovarian carcinoma tissues from Mexican patients.
abstract: BACKGROUND
  Ovarian cancer is the most lethal gynecologic disease due to delayed diagnosis, and ascites production is a characteristic of patients in advanced stages. The aim of this study was to perform the proteomic analysis of ascitic fluids of Mexican patients with ovarian carcinoma, in order to detect proteins with a differential expression pattern in the continuing search to identify biomarkers for this disease.
  
  
  METHODS
  Samples were collected from 50 patients from the Instituto Nacional de Cancerología of México under informed consent and with approval of the bioethics and scientific committees. After elimination of abundant proteins (Albumin/IgGs) samples were processed for 2D electrophoresis and further protein identification by Mass Spectrometry (MALDI-TOF). Molecules of interest were followed by western blot and lectin binding assays, and their tissue location by histo-immunofluorescence and confocal analysis.
  
  
  CONCLUSIONS
  An area with a differential expression pattern among samples was located in the 2D gels. Identified proteins were 6 alpha 1 isoforms and 1 alpha 2 isoform of Haptoglobin, and 2 isoforms of Transthyretin. While Transthyretin isoforms were constitutively expressed in all samples, clear differences in the expression pattern of Haptoglobin alpha isoforms were found. Moreover, increased levels of fucosylation of Haptoglobin alpha isoforms analyzed in 40 samples by Aleuria aurantia lectin binding by 1D overlay assay showed a positive correlation with advanced stages of the disease. Tissue detection of Haptoglobin and its fucosylated form, by histo-immunofluorescence in biopsies of ovarian cancer, also showed a correlation with ovarian cancer progression. Moreover, results show that fucosylated Haptoglobin is produced by tumor cells.
  
  
  CONCLUSIONS
  Increased numbers of highly fucosylated Haptoglobin alpha isoforms in ascitic fluids and the presence of fucosylated Haptoglobin in tumor tissues of ovarian cancer Mexican patients associated with advanced stages of the disease, reinforce the potential of fucosylated Haptoglobin alpha isoforms to be characterized as biomarkers for disease progression.
authors.forename: Olga Lilia
authors.initials: OL
authors.lastname: Garibay-Cerdenares
authors.forename: Verónica Ivonne
authors.initials: VI
authors.lastname: Hernández-Ramírez
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Osorio-Trujillo
authors.forename: Magdalena
authors.initials: M
authors.lastname: Hernández-Ortíz
authors.forename: Dolores
authors.initials: D
authors.lastname: Gallardo-Rincón
authors.forename: David
authors.initials: D
authors.lastname: Cantú de León
authors.forename: Sergio
authors.initials: S
authors.lastname: Encarnación-Guevara
authors.forename: Julio César
authors.initials: JC
authors.lastname: Villegas-Pineda
authors.affiliation: Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Av, Instituto Politécnico Nacional 2508, Col, San Pedro Zacatenco, Delegación Gustavo A, Madero, México, D,F, 07360, México. ptr@cinvestav.mx.
authors.forename: Patricia
authors.initials: P
authors.lastname: Talamás-Rohana
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001202:Ascitic Fluid / Q000737:chemistry*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002277:Carcinoma / Q000737:chemistry* / Q000473:pathology; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D005455:Fluorescent Antibody Technique; D005643:Fucose / Q000032:analysis*; D006242:Haptoglobins / Q000032:analysis*; D006801:Humans; D008800:Mexico; D018613:Microscopy, Confocal; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000473:pathology; D011237:Predictive Value of Tests; D020033:Protein Isoforms; D040901:Proteomics / Q000379:methods; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C485359:HP protein, human; D006242:Haptoglobins; D020033:Protein Isoforms; D005643:Fucose