title: Protein expression changes in ovarian cancer during the transition from benign to malignant.
abstract: Epithelial ovarian carcinoma has in general a poor prognosis since the vast majority of tumors are genomically unstable and clinically highly aggressive. This results in rapid progression of malignancy potential while still asymptomatic and thus in late diagnosis. It is therefore of critical importance to develop methods to diagnose epithelial ovarian carcinoma at its earliest developmental stage, that is, to differentiate between benign tissue and its early malignant transformed counterparts. Here we present a shotgun quantitative proteomic screen of benign and malignant epithelial ovarian tumors using iTRAQ technology with LC-MALDI-TOF/TOF and LC-ESI-QTOF MS/MS. Pathway analysis of the shotgun data pointed to the PI3K/Akt signaling pathway as a significant discriminatory pathway. Selected candidate proteins from the shotgun screen were further confirmed in 51 individual tissue samples of normal, benign, borderline or malignant origin using LC-MRM analysis. The MRM profile demonstrated significant differences between the four groups separating the normal tissue samples from all tumor groups as well as perfectly separating the benign and malignant tumors with a ROC-area of 1. This work demonstrates the utility of using a shotgun approach to filter out a signature of a few proteins only that discriminates between the different sample groups.
authors.affiliation: Department of Immunotechnology, Lund University, BMC D13, 221 84 Lund, Sweden. sofia.waldemarson@immun.lth.se
authors.forename: Sofia
authors.initials: S
authors.lastname: Waldemarson
authors.forename: Morten
authors.initials: M
authors.lastname: Krogh
authors.forename: Ayodele
authors.initials: A
authors.lastname: Alaiya
authors.forename: Ufuk
authors.initials: U
authors.lastname: Kirik
authors.forename: Kjell
authors.initials: K
authors.lastname: Schedvins
authors.forename: Gert
authors.initials: G
authors.lastname: Auer
authors.forename: Karin M
authors.initials: KM
authors.lastname: Hansson
authors.forename: Reto
authors.initials: R
authors.lastname: Ossola
authors.forename: Ruedi
authors.initials: R
authors.lastname: Aebersold
authors.forename: Hookeun
authors.initials: H
authors.lastname: Lee
authors.forename: Johan
authors.initials: J
authors.lastname: Malmström
authors.forename: Peter
authors.initials: P
authors.lastname: James
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000032:analysis / Q000378:metabolism*; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D020543:Proteome / Q000032:analysis / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D012372:ROC Curve; D020539:Sequence Analysis, Protein; D015398:Signal Transduction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D014407:Tumor Cells, Cultured
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D020543:Proteome; C572235:YWHAZ protein, human; D019869:Phosphatidylinositol 3-Kinases