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HDAC2 and TXNL1 distinguish aneuploid from diploid colorectal cancers
Authors:Gemoll Timo  Roblick Uwe J  Szymczak Silke  Braunschweig Till  Becker Susanne  Igl Bernd-Wolfgang  Bruch Hans-Peter  Ziegler Andreas  Hellman Ulf  Difilippantonio Michael J  Ried Thomas  Jörnvall Hans  Auer Gert  Habermann Jens K
Institution:1. Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 17177, Stockholm, Sweden
2. Laboratory for Surgical Research, Department of Surgery, University of L??beck, Ratzeburger Allee 160, 23538, L??beck, Germany
3. Karolinska Biomic Center, Karolinska Institutet, 17176, Stockholm, Sweden
5. Institute for Medical Biometry and Statistics, University of L??beck, 23538, L??beck, Germany
4. Institute for Pathology, University Clinic RWTH Aachen, 52074, Aachen, Germany
6. Ludwig Institute for Cancer Research Ltd., 75124, Uppsala, Sweden
7. Department of Genetics, Center for Cancer Research, NCI/NIH, Bethesda, MD, 20814, USA
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.
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