title: A serum based analysis of ovarian epithelial tumorigenesis.
abstract: OBJECTIVE
  Ovarian epithelial carcinoma can be subdivided into separate histological subtypes including clear cell, endometrioid, mucinous, and serous. These carcinoma subtypes may represent distinctive pathways of tumorigenesis and disease development. This distinction could potentially be reflected in the levels of tumor produced factors that enter into the circulation and serve as biomarkers of malignant growth. Here, we analyze levels of circulating biomarkers from a diverse set of patients diagnosed with ovarian carcinoma to identify biomarker trends and relationships associated with distinct carcinoma histotypes and divergent tumorigenic pathways.
  
  
  METHODS
  We utilize multiplexed bead-based immunoassays to measure serum levels of a diverse array of fifty-eight biomarkers from the sera of patients diagnosed with various histological subtypes of ovarian carcinoma and benign lesions. The biomarkers studied include cancer antigens, oncogenes, cytokines, chemokines, receptors, growth and angiogenic factors, proteases, hormones, and apoptosis and adhesion related molecules. Levels of each biomarker are compared statistically across carcinoma subtypes as well as with benign cases.
  
  
  RESULTS
  A total of 21 serum biomarkers differ significantly between patients diagnosed with ovarian carcinomas and benign cases. Nine of these biomarkers are specific for carcinomas identified as clear cell, endometrioid, or mucinous in histology, while two biomarkers are specific for the serous histology. In a direct comparison of the histology groups, ten biomarkers are found to be subtype specific. Identified biomarkers include traditional and emerging tumor markers, cytokines and receptors, hormones, and adhesion- and metastasis-related proteins.
  
  
  CONCLUSIONS
  We demonstrate here that the divergent histology-based tumorigenic pathways proposed for ovarian epithelial carcinomas are associated with distinct profiles of circulating biomarkers. Continued investigation into the relationships between these factors should reveal new insights into the complex mechanisms underlying ovarian epithelial tumorigenesis.
authors.affiliation: University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, PA 15213, USA. nolanb@upmc.edu
authors.forename: Brian
authors.initials: B
authors.lastname: Nolen
authors.forename: Adele
authors.initials: A
authors.lastname: Marrangoni
authors.forename: Liudmila
authors.initials: L
authors.lastname: Velikokhatnaya
authors.forename: Denise
authors.initials: D
authors.lastname: Prosser
authors.forename: Matthew
authors.initials: M
authors.lastname: Winans
authors.forename: Elesier
authors.initials: E
authors.lastname: Gorelik
authors.forename: Anna
authors.initials: A
authors.lastname: Lokshin
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000097:blood / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000097:blood / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D018269:Carcinoma, Endometrioid / Q000097:blood / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000097:blood* / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor