title: Association between protein C levels and mortality in patients with advanced prostate, lung and pancreatic cancer.
abstract: BACKGROUND
  Procoagulant factors promote cancer progression and metastasis. Protein C is involved in hemostasis, inflammation and signal transduction, and has a protective effect on the endothelial barrier. In mice, administration of activated protein C reduced experimental metastasis. We assessed the association between protein C and mortality in patients with three types of cancer.
  
  
  METHODS
  The study population consisted of patients with advanced prostate, non-small cell lung or pancreatic cancer, who participated in the INPACT trial (NCT00312013). The trial evaluated the addition of nadroparin to chemotherapy in patients with advanced malignancy. Patients were divided into tertiles based on protein C at baseline. The association between protein C levels and mortality was evaluated with Cox proportional hazard models.
  
  
  RESULTS
  We analysed 477 patients (protein C tertiles: <97, 97-121 and ≥121%). Mean age was 65±9years; 390 (82%) were male; 191 patients (40%) had prostate cancer, 161 (34%) had lung cancer, and 125 (26%) pancreatic cancer. During a median follow-up of 10.4months, 291 patients (61%) died. Median protein C level was 107% (IQR 92-129). In the lowest tertile, 75 patients per 100 patient-years died, as compared to 60 and 54 in the middle and high tertile, respectively. Lower levels of protein C were associated with increased mortality (in tertiles: HR for trend 1.18, 95%CI 1.02-1.36, adjusted for age, sex and nadroparin use; as a continuous variable: HR 1.004, 95%CI 1.00-1.008, p=0.07).
  
  
  CONCLUSIONS
  Protein C seems inversely associated with mortality in patients with advanced prostate, lung and pancreatic cancer. Further research should validate protein C as a biomarker for mortality, and explore the effects of protein C on progression of cancer.
authors.affiliation: Department of Vascular Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Electronic address: i.t.wilts@umcg.nl.
authors.forename: I T
authors.initials: IT
authors.lastname: Wilts
authors.affiliation: Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: b.a.hutten@amc.nl.
authors.forename: B A
authors.initials: BA
authors.lastname: Hutten
authors.affiliation: Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands; Department of Plasma Proteins, Sanquin Research, Amsterdam, The Netherlands. Electronic address: j.c.meijers@amc.nl.
authors.forename: J C M
authors.initials: JCM
authors.lastname: Meijers
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: c.a.spek@amc.nl.
authors.forename: C A
authors.initials: CA
authors.lastname: Spek
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands. Electronic address: h.r.buller@amc.nl.
authors.forename: H R
authors.initials: HR
authors.lastname: Büller
authors.affiliation: Department of Vascular Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Tergooi Hospital, Hilversum, The Netherlands. Electronic address: p.w.kamphuisen@umcg.nl.
authors.forename: P W
authors.initials: PW
authors.lastname: Kamphuisen
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008875:Middle Aged; D017762:Nadroparin / Q000627:therapeutic use; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D011486:Protein C / Q000032:analysis*
chemical_list: D000925:Anticoagulants; D014408:Biomarkers, Tumor; D017762:Nadroparin; D011486:Protein C
keywords: Biomarker; Cancer; Coagulation; Protein C