title: The serine protease prostasin (PRSS8) is a potential biomarker for early detection of ovarian cancer.
abstract: BACKGROUND
  Ovarian cancer (OVC) is the deadliest of all gynecologic cancers, primarily as a consequence of asymptomatic progression. The complex nature of OVC creates challenges for early detection, and there is a lack of specific and sensitive biomarkers suitable for screening and detecting early stage OVC.
  
  
  METHODS
  Potential OVC biomarkers were identified by bioinformatic analysis. Candidates were further screened for differential expression in a library of OVC cell lines. OVC-specific overexpression of a candidate gene, PRSS8, which encodes prostasin, was confirmed against 18 major human cancer types from 390 cancer samples by qRT-PCR. PRSS8 expression profiles stratified by OVC tumor stage-, grade- and subtype were generated using cDNA samples from 159 OVC samples. Cell-specific expression and localization of prostasin was determined by immunohistological tissue array analysis of more than 500 normal, benign, and cancerous ovarian tissues. The presence of prostasin in normal, benign, and OVC serum samples was also determined.
  
  
  RESULTS
  Gene expression analysis indicated that PRSS8 was expressed in OVC at levels more than 100 fold greater than found in normal or benign ovarian lesions. This overexpression signature was found in early stages of OVC and was maintained in higher stages and grades of OVC. The PRSS8 overexpression signature was specific for OVC and urinary bladder cancer among 18 human cancer types. The majority of ovarian cell lines overexpressed PRSS8. In situ hybridization and histopathology studies of OVC tissues indicated that overexpression of prostasin was largely localized to tumor epithelium and was absent in neighboring stroma. Significantly higher levels of prostasin were found in early stage OVC serum samples compared to benign ovarian and normal donor samples.
  
  
  CONCLUSIONS
  The abundant amounts of secreted prostasin found in sera of early stage OVC can potentially be used as a minimally invasive screening biomarker for early stage OVC. Overexpression of PRSS8 mRNA and high levels of prostasin in multiple subtypes of early stage ovarian tumors may provide clinical biomarkers for early detection of OVC, which can potentially be used with CA125 and HE4.
authors.affiliation: The Genomics and Biomarkers Program, The John Theurer Cancer Center, Hackensack University Medical Center, D. Jurist Research Building, 40 Prospect Avenue, Hackensack, NJ, 07601, USA.
authors.forename: Ayala
authors.initials: A
authors.lastname: Tamir
authors.affiliation: The Genomics and Biomarkers Program, The John Theurer Cancer Center, Hackensack University Medical Center, D. Jurist Research Building, 40 Prospect Avenue, Hackensack, NJ, 07601, USA.
authors.forename: Anju
authors.initials: A
authors.lastname: Gangadharan
authors.affiliation: The Genomics and Biomarkers Program, The John Theurer Cancer Center, Hackensack University Medical Center, D. Jurist Research Building, 40 Prospect Avenue, Hackensack, NJ, 07601, USA.
authors.forename: Sakshi
authors.initials: S
authors.lastname: Balwani
authors.affiliation: Stephenson Cancer Center, University of Oklahoma Health Science Center, Oklahoma city, OK, 73104, USA.
authors.forename: Takemi
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: The Genomics and Biomarkers Program, The John Theurer Cancer Center, Hackensack University Medical Center, D. Jurist Research Building, 40 Prospect Avenue, Hackensack, NJ, 07601, USA.
authors.forename: Ushma
authors.initials: U
authors.lastname: Patel
authors.affiliation: The Genomics and Biomarkers Program, The John Theurer Cancer Center, Hackensack University Medical Center, D. Jurist Research Building, 40 Prospect Avenue, Hackensack, NJ, 07601, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Hassan
authors.affiliation: The Genomics and Biomarkers Program, The John Theurer Cancer Center, Hackensack University Medical Center, D. Jurist Research Building, 40 Prospect Avenue, Hackensack, NJ, 07601, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Benke
authors.affiliation: The Genomics and Biomarkers Program, The John Theurer Cancer Center, Hackensack University Medical Center, D. Jurist Research Building, 40 Prospect Avenue, Hackensack, NJ, 07601, USA.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Agas
authors.affiliation: The Genomics and Biomarkers Program, The John Theurer Cancer Center, Hackensack University Medical Center, D. Jurist Research Building, 40 Prospect Avenue, Hackensack, NJ, 07601, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: D'Agostino
authors.affiliation: The Genomics and Biomarkers Program, The John Theurer Cancer Center, Hackensack University Medical Center, D. Jurist Research Building, 40 Prospect Avenue, Hackensack, NJ, 07601, USA.
authors.forename: Dayoung
authors.initials: D
authors.lastname: Shin
authors.affiliation: The Genomics and Biomarkers Program, The John Theurer Cancer Center, Hackensack University Medical Center, D. Jurist Research Building, 40 Prospect Avenue, Hackensack, NJ, 07601, USA.
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Yoon
authors.affiliation: Clinical Divisions, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, 07601, USA.
authors.forename: Andre
authors.initials: A
authors.lastname: Goy
authors.affiliation: Clinical Divisions, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, 07601, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Pecora
authors.affiliation: The Genomics and Biomarkers Program, The John Theurer Cancer Center, Hackensack University Medical Center, D. Jurist Research Building, 40 Prospect Avenue, Hackensack, NJ, 07601, USA. KSuh@HackensackUMC.org.
authors.forename: K Stephen
authors.initials: KS
authors.lastname: Suh
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D055088:Early Detection of Cancer; D005260:Female; D015870:Gene Expression; D006801:Humans; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis / Q000201:enzymology*; D012697:Serine Endopeptidases / Q000097:blood* / Q000235:genetics; D000099271:Prostasin
chemical_list: D014408:Biomarkers, Tumor; D012697:Serine Endopeptidases; D000099271:Prostasin
keywords: Biomarkers; Diagnostic; Early detection; Ovarian cancer; PRSS8; Prostasin; Serum