title: A Strong Neutrophil Elastase Proteolytic Fingerprint Marks the Carcinoma Tumor Proteome.
abstract: Proteolytic cascades are deeply involved in critical stages of cancer progression. During the course of peptide-wise analysis of shotgun proteomic data sets representative of colon adenocarcinoma (AC) and ulcerative colitis (UC), we detected a cancer-specific proteolytic fingerprint composed of a set of numerous protein fragments cleaved C-terminally to V, I, A, T, or C residues, significantly overrepresented in AC. A peptide set linked by a common VIATC cleavage consensus was the only prominent cancer-specific proteolytic fingerprint detected. This sequence consensus indicated neutrophil elastase as a source of the fingerprint. We also found that a large fraction of affected proteins are RNA processing proteins associated with the nuclear fraction and mostly cleaved within their functionally important RNA-binding domains. Thus, we detected a new class of cancer-specific peptides that are possible markers of tumor-infiltrating neutrophil activity, which often correlates with the clinical outcome. Data are available via ProteomeXchange with identifiers: PXD005274 (Data set 1) and PXD004249 (Data set 2). Our results indicate the value of peptide-wise analysis of large global proteomic analysis data sets as opposed to protein-wise analysis, in which outlier differential peptides are usually neglected.
authors.affiliation: From the ‡Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5A, 02-106 Warsaw.
authors.forename: Michał
authors.initials: M
authors.lastname: Kistowski
authors.affiliation: From the ‡Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5A, 02-106 Warsaw.
authors.forename: Janusz
authors.initials: J
authors.lastname: Dębski
authors.affiliation: §Department of Genetics, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Wilhelma Konrada Roentgena 5, 02-781 Warsaw, Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Karczmarski
authors.affiliation: §Department of Genetics, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Wilhelma Konrada Roentgena 5, 02-781 Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Paziewska
authors.affiliation: From the ‡Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5A, 02-106 Warsaw.
authors.forename: Jacek
authors.initials: J
authors.lastname: Olędzki
authors.affiliation: §Department of Genetics, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Wilhelma Konrada Roentgena 5, 02-781 Warsaw, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Mikula
authors.affiliation: ¶Department of Gastroenterology Hepatology and Clinical Oncology, Medical Center for Postgraduate Education, Warsaw, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Ostrowski
authors.affiliation: From the ‡Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5A, 02-106 Warsaw; michald@ibb.waw.pl.
authors.forename: Michał
authors.initials: M
authors.lastname: Dadlez
mesh_terms: D003110:Colonic Neoplasms / Q000378:metabolism*; D030562:Databases, Protein; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism*; D010455:Peptides / Q000032:analysis*; D060066:Protein Interaction Maps; D059748:Proteolysis; D040901:Proteomics / Q000379:methods*
chemical_list: D010455:Peptides; D019272:Leukocyte Elastase