title: Fully-sialylated alpha-chain of complement 4-binding protein: Diagnostic utility for ovarian clear cell carcinoma.
abstract: OBJECTIVE
  While a certain fraction of endometriomas can develop de novo epithelial ovarian cancer (EOC) such as clear cell carcinoma (OCCC), there is currently no useful biomarker available for early detection of OCCC from endometriomas. The aim of this study was to describe the diagnostic utility of a novel biomarker for EOC especially for OCCC to distinguish from endometrioma.
  
  
  METHODS
  More than 100,000 glycan structures of serum glycoproteins obtained from 134 pretreatment all stage EOC patients (including 45 OCCCs) and 159 non-cancer control women (including 36 endometriomas) were explored for a mass spectrum approach. Diagnostic accuracy of identified biomarker was compared to the one of CA-125 by comparing area under curve (AUC) and positive/negative predictive values (PPV and NPV).
  
  
  RESULTS
  A2160, a fully-sialylated alpha-chain of complement 4-binding protein, was identified as a candidate target marker. A2160 was significantly elevated in all stages of OCCC compared to with endometriomas. Diagnostic accuracy of A2160 (cutoff 1.6U/mL) to distinguish early stage OCCC from endometrioma is significantly higher than that of CA-125 (cutoff 35IU/L): AUC for A2160 versus CA-125, 0.92 versus 0.67; PPV 95% versus 64%; and NPV 85% versus 58%. In addition, fully-sialylated glycans had a higher accuracy for diagnosing EOC as compared to partially-sialylated glycans of alpha-chain of complement 4-binding protein.
  
  
  CONCLUSIONS
  Our study suggested that A2160 may be a useful biomarker to distinguish early-stage OCCC from endometrioma. This new biomarker can be potentially applied for the monitoring of endometrioma patients, making possible the early diagnosis of OCCC.
authors.affiliation: Department of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa 2591193, Japan. Electronic address: mmikami@is.icc.u-tokai.ac.jp.
authors.forename: Mikio
authors.initials: M
authors.lastname: Mikami
authors.affiliation: Advanced Technology Center, Medical Solution Segment, LSI Medience Corporation, Tokyo 1748555, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tanabe
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles 90033, USA.
authors.forename: Koji
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Advanced Technology Center, Medical Solution Segment, LSI Medience Corporation, Tokyo 1748555, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Miyazaki
authors.affiliation: Department of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa 2591193, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Miyazawa
authors.affiliation: Department of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa 2591193, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Department of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa 2591193, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Asai
authors.affiliation: Department of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa 2591193, Japan.
authors.forename: Masae
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Department of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa 2591193, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Shida
authors.affiliation: Department of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa 2591193, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hirasawa
authors.affiliation: Mitsubishi Chemical Group Science and Technology Research Center, Inc., Yokohama 2278502, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Kojima
authors.affiliation: Department of Obstetrics and Gynecology, Sho Hospital, Tokyo 1730004, Japan.
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Sho
authors.affiliation: International Sales Department, LSI Medience Corporation, Tokyo 1018517, Japan.
authors.forename: Sadayo
authors.initials: S
authors.lastname: Iijima
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000097:blood* / Q000473:pathology*; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000378:metabolism*; D018394:CA-125 Antigen / Q000097:blood; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D050716:Complement C4b-Binding Protein / Q000737:chemistry / Q000378:metabolism*; D004715:Endometriosis / Q000097:blood; D005260:Female; D006020:Glycopeptides / Q000097:blood*; D006801:Humans; D013058:Mass Spectrometry; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000097:blood* / Q000473:pathology*; D011237:Predictive Value of Tests; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor; C055609:C4BPA protein, human; D018394:CA-125 Antigen; D050716:Complement C4b-Binding Protein; D006020:Glycopeptides
keywords: Complement 4-binding protein; Endometrioma: early detection; Full sialylation; Ovarian clear cell carcinoma