title: Utility of progranulin and serum leukocyte protease inhibitor as diagnostic and prognostic biomarkers in ovarian cancer.
abstract: BACKGROUND
  Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer-related death in females and leading gynecologic cause of cancer-related death. Despite the identification of a number of serum biomarkers, methods to identify early-stage disease and predict prognosis remain scarce. We have evaluated two biologically connected serum biomarkers, serum leukocyte protease inhibitor (SLPI) and progranulin (PGRN).
  
  
  METHODS
  Two-hundred frozen plasma samples were acquired from the Mayo Clinic Biospecimen Repository for Ovarian Cancer Research. Samples were obtained from 50 patients with benign conditions, 50 with American Joint Committee on Cancer (AJCC) stage I and II EOC, and 100 with AJCC stage III and IV EOC. Samples were obtained before surgical resection of a mass and were analyzed for absolute levels of SLPI and PGRN using ELISA assays. Receiver-operator characteristic curves were generated for SLPI and PGRN. Median follow-up was 48 months.
  
  
  RESULTS
  Absolute levels of SLPI were significantly elevated in patients with EOC compared with benign disease and predicted the presence of EOC (AUC of 0.812; P = 0.04); SLPI remained elevated in the subset of patients with normal CA-125. PGRN levels were not significantly increased in patients with early-stage or late-stage EOC as a whole, but an increase in PGRN levels was associated with decreased overall survival in advanced EOC.
  
  
  CONCLUSIONS
  SLPI levels are elevated in EOC, and SLPI shows promise as a diagnostic biomarker for patients with both elevated and normal CA-125 levels. An increase in PGRN is associated with decreased overall survival.
  
  
  CONCLUSIONS
  SLPI is elevated in EOC and warrants investigation in a screening study in women at risk for EOC.
authors.affiliation: Authors' Affiliations: Mayo Medical School, Biomedical Statistics and Informatics, and Departments of Medical Oncology and Immunology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Carlson
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Maurer
authors.forename: Krista M
authors.initials: KM
authors.lastname: Goergen
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Kalli
authors.forename: Courtney L
authors.initials: CL
authors.lastname: Erskine
authors.forename: Marshall D
authors.initials: MD
authors.lastname: Behrens
authors.forename: Keith L
authors.initials: KL
authors.lastname: Knutson
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Block
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D000077216:Carcinoma, Ovarian Epithelial; D015331:Cohort Studies; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000235:genetics; D007962:Leukocytes / Q000378:metabolism*; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood*; D010051:Ovarian Neoplasms / Q000097:blood*; D011379:Prognosis; D000077153:Progranulins; D011480:Protease Inhibitors / Q000097:blood*; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000097:blood*; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D011480:Protease Inhibitors; D053481:Secretory Leukocyte Peptidase Inhibitor