title: HDAC2 and TXNL1 distinguish aneuploid from diploid colorectal cancers.
abstract: DNA aneuploidy has been identified as a prognostic factor for epithelial malignancies. Further understanding of the translation of DNA aneuploidy into protein expression will help to define novel biomarkers to improve therapies and prognosis. DNA ploidy was assessed by image cytometry. Comparison of gel-electrophoresis-based protein expression patterns of three diploid and four aneuploid colorectal cancer cell lines detected 64 ploidy-associated proteins. Proteins were identified by mass spectrometry and subjected to Ingenuity Pathway Analysis resulting in two overlapping high-ranked networks maintaining Cellular Assembly and Organization, Cell Cycle, and Cellular Growth and Proliferation. CAPZA1, TXNL1, and HDAC2 were significantly validated by Western blotting in cell lines and the latter two showed expression differences also in clinical samples using a tissue microarray of normal mucosa (n=19), diploid (n=31), and aneuploid (n=47) carcinomas. The results suggest that distinct protein expression patterns, affecting TXNL1 and HDAC2, distinguish aneuploid with poor prognosis from diploid colorectal cancers.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177 Stockholm, Sweden.
authors.forename: Timo
authors.initials: T
authors.lastname: Gemoll
authors.forename: Uwe J
authors.initials: UJ
authors.lastname: Roblick
authors.forename: Silke
authors.initials: S
authors.lastname: Szymczak
authors.forename: Till
authors.initials: T
authors.lastname: Braunschweig
authors.forename: Susanne
authors.initials: S
authors.lastname: Becker
authors.forename: Bernd-Wolfgang
authors.initials: BW
authors.lastname: Igl
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Bruch
authors.forename: Andreas
authors.initials: A
authors.lastname: Ziegler
authors.forename: Ulf
authors.initials: U
authors.lastname: Hellman
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Difilippantonio
authors.forename: Thomas
authors.initials: T
authors.lastname: Ried
authors.forename: Hans
authors.initials: H
authors.lastname: Jörnvall
authors.forename: Gert
authors.initials: G
authors.lastname: Auer
authors.forename: Jens K
authors.initials: JK
authors.lastname: Habermann
mesh_terms: D000782:Aneuploidy; D015153:Blotting, Western; D051347:CapZ Actin Capping Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000737:chemistry; D004171:Diploidy; D042822:Genomic Instability; D056464:Histone Deacetylase 2 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D011379:Prognosis; D013879:Thioredoxins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
chemical_list: C495842:CAPZA1 protein, human; D051347:CapZ Actin Capping Protein; D004273:DNA, Neoplasm; C504766:TXNL1 protein, human; D013879:Thioredoxins; C533423:HDAC2 protein, human; D056464:Histone Deacetylase 2