title: Discovery of novel plasma proteins as biomarkers for the development of incisional hernias after midline incision in patients with colorectal cancer: The ColoCare study.
abstract: Ventral incisional hernia is the most common long-term complication after an abdominal operation. Among newly diagnosed colorectal cancer patients, we screened the preoperative plasma proteome to explore predictive markers for the development of an incisional hernia.
  
  
  
  We utilized preoperative plasma samples of 72 newly diagnosed colorectal cancer patients who underwent midline incision for tumor resection between 2010 and 2013. A total of 21 patients with incisional hernia occurrence were matched with 51 patients with at least 18 months follow-up without an incisional hernia by sex, age, and body mass index. To assess predictive markers of incisional hernia risk, we screened the plasma proteome for >2,000 distinct proteins using a well-validated antibody microarray test. Paired t tests were used to compare protein levels between cases and controls. A gene-set-enrichment analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) was applied to test for differences in signaling pathways between the 2 groups.
  
  
  
  The proteome screen identified 25 proteins that showed elevated or reduced plasma levels in the hernia group compared to the control group (nominal P values < .05). Several proteins were in pathways associated with wound healing (CCL21, SHBG, BRF2) or cell adhesion (PCDH15, CDH3, EPCAM).
  
  
  
  Our study shows that there are multiple individual and groups of plasma proteins that could feasibly predict the personal hernia risk prior to undergoing an operation. Further investigations in larger, independent sample sets are warranted to replicate findings and validate clinical utility of potential biomarkers. After validation, such a biomarker could be incorporated into a multifactorial risk model to guide clinical decision-making.
authors.affiliation: Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah School of Medicine, Salt Lake City, UT.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Böhm
authors.affiliation: Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Pianka
authors.affiliation: Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Stüttgen
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Junghyun
authors.initials: J
authors.lastname: Rho
authors.affiliation: Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Biljana
authors.initials: B
authors.lastname: Gigic
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Yuzheng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Genome Biology, European Molecular Biology Laboratory, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Habermann
authors.affiliation: Division of Preventive Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Schrotz-King
authors.affiliation: Division of Preventive Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany.
authors.forename: Clare
authors.initials: C
authors.lastname: Abbenhardt-Martin
authors.affiliation: Division of Preventive Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany.
authors.forename: Lin
authors.initials: L
authors.lastname: Zielske
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Lampe
authors.affiliation: Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Alexis
authors.initials: A
authors.lastname: Ulrich
authors.affiliation: Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Markus K
authors.initials: MK
authors.lastname: Diener
authors.affiliation: Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah School of Medicine, Salt Lake City, UT. Electronic address: neli.ulrich@hci.utah.edu.
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Ulrich
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood* / Q000601:surgery; D005260:Female; D006801:Humans; D000069290:Incisional Hernia / Q000097:blood* / Q000209:etiology*; D007813:Laparotomy / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011183:Postoperative Complications / Q000097:blood* / Q000209:etiology
chemical_list: D015415:Biomarkers; D001798:Blood Proteins