title: Absolute Proteome Analysis of Colorectal Mucosa, Adenoma, and Cancer Reveals Drastic Changes in Fatty Acid Metabolism and Plasma Membrane Transporters.
abstract: Colorectal cancer is a leading cause of cancer-related death. It develops from normal enterocytes, through a benign adenoma stage, into the cancer and finally into the metastatic form. We previously compared the proteomes of normal colorectal enterocytes, cancer and nodal metastasis to a depth of 8100 proteins and found extensive quantitative remodeling between normal and cancer tissues but not cancer and metastasis (Wiśniewski et al. PMID 22968445). Here we utilize advances in the proteomic workflow to perform an in depth analysis of the normal tissue (N), the adenoma (A), and the cancer (C). Absolute proteomics of 10 000 proteins per patient from microdissected formalin-fixed and paraffin-embedded clinical material established a quantitative protein repository of the disease. Between N and A, 23% of all proteins changed significantly, 17.8% from A to C and 21.6% from N to C. Together with principal component analysis of the patient groups, this suggests that N, A, and C are equidistant but not on one developmental line. Our proteomics approach allowed us to assess changes in varied cell size, the composition of different subcellular components, and alterations in basic biological processes including the energy metabolism, plasma membrane transport, DNA replication, and transcription. This revealed several-fold higher concentrations of enzymes in fatty acid metabolism in C compared with N, and unexpectedly, the same held true of plasma membrane transporters.
authors.affiliation: Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry , Am Klopferspitz 18, 82152 Martinsried, Germany.
authors.forename: Jacek R
authors.initials: JR
authors.lastname: Wiśniewski
authors.affiliation: Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry , Am Klopferspitz 18, 82152 Martinsried, Germany.|Department of Pathology, Wrocław Medical University , 50-368 Wrocław, Poland.
authors.forename: Kamila
authors.initials: K
authors.lastname: Duś-Szachniewicz
authors.affiliation: Department of Pathology, Wrocław Medical University , 50-368 Wrocław, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Ostasiewicz
authors.affiliation: Department of Pathology, Wrocław Medical University , 50-368 Wrocław, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Ziółkowski
authors.affiliation: Department of Animal Molecular Physiology, Wroclaw University , 50-205 Wrocław, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Rakus
authors.affiliation: Department of Proteomics and Signal Transduction, Max-Planck-Institute of Biochemistry , Am Klopferspitz 18, 82152 Martinsried, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
mesh_terms: D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005227:Fatty Acids / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D061346:Laser Capture Microdissection; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism*; D020543:Proteome / Q000032:analysis*; D040901:Proteomics
chemical_list: D005227:Fatty Acids; D008565:Membrane Proteins; D020543:Proteome
keywords: FASP; FFPE-tissue; absolute protein quantification; adenomatous polyposis coli; colorectal cancer; enterocyte; metabolism; quantitative proteomics; total protein approach