title: Clinical Significance of Tissue Factor Pathway Inhibitor 2, a Serum Biomarker Candidate for Ovarian Clear Cell Carcinoma.
abstract: BACKGROUND
  There is currently no reliable serum biomarker for ovarian clear cell carcinoma (CCC), a highly lethal histological subtype of epithelial ovarian cancer (EOC). Previously, using a proteome-based approach, we identified tissue factor pathway inhibitor 2 (TFPI2) as a candidate serum biomarker for CCC. In this study, we sought to evaluate the clinical diagnostic performance of TFPI2 in preoperative prediction of CCC.
  
  
  METHODS
  Serum TFPI2 levels were measured in serum samples from a retrospective training set consisting of patients with benign and borderline ovarian tumors, EOC subtypes, and uterine diseases. Via receiver operating characteristic (ROC) analyses, we compared the diagnostic performance of TFPI2 with that of CA125 in discrimination of patients with ovarian CCC from other patient groups. The observed diagnostic performances were examined in a prospective validation set.
  
  
  RESULTS
  The 268-patient training set included 29 patients with ovarian CCC. Unlike CA125, which was also elevated in patients with endometriosis and several EOC subtypes, serum TFPI2 levels were specifically elevated only in ovarian CCC patients, consistent with the mRNA expression pattern in tumor tissues. The area under the ROC curve (AUC) of serum TFPI2 was obviously higher than that of CA125 for discrimination of CCC from other ovarian diseases (AUC = 0.891 versus 0.595). Applying a cut-off value of 280 pg/mL, TFPI2 could distinguish early-stage (FIGO I and II) CCC from endometriosis with 72.2% sensitivity, 93.3% specificity, and 88.8% accuracy. Similar results were confirmed in an independent 156-patient prospective validation set.
  
  
  CONCLUSIONS
  TFPI2 is a useful serum biomarker for preoperative clinical diagnosis of CCC.
authors: Department of Medical Life Science, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Kanagawa, Japan.|Advanced Medical Research Center, Yokohama City University, Yokohama, Kanagawa, Japan.
authors: Noriaki
authors: N
authors: Arakawa
authors: Department of Obstetrics and Gynecology, Nara Medical University, Nara, Japan.
authors: Hiroshi
authors: H
authors: Kobayashi
authors: Department of Biostatistics, Center for Novel and Explanatory Clinical Trials (Y-NEXT), Yokohama City University, Yokohama, Kanagawa, Japan.
authors: Naohiro
authors: N
authors: Yonemoto
authors: Department of Medical Life Science, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Kanagawa, Japan.|Advanced Medical Research Center, Yokohama City University, Yokohama, Kanagawa, Japan.
authors: Yusuke
authors: Y
authors: Masuishi
authors: Department of Medical Life Science, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Kanagawa, Japan.|Advanced Medical Research Center, Yokohama City University, Yokohama, Kanagawa, Japan.
authors: Yoko
authors: Y
authors: Ino
authors: Department of Obstetrics and Gynecology, Nara Medical University, Nara, Japan.
authors: Hiroshi
authors: H
authors: Shigetomi
authors: Department of Obstetrics and Gynecology, Nara Medical University, Nara, Japan.
authors: Naoto
authors: N
authors: Furukawa
authors: Bioscience Division, Reagent Development Department, Tosoh Corporation, Ayase, Kanagawa, Japan.
authors: Norihisa
authors: N
authors: Ohtake
authors: Research Institute, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan.
authors: Yohei
authors: Y
authors: Miyagi
authors: Yokohama City University Hospital, Department of Obstetrics and Gynecology, Yokohama, Kanagawa, Japan.
authors: Fumiki
authors: F
authors: Hirahara
authors: Department of Medical Life Science, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Kanagawa, Japan.|Advanced Medical Research Center, Yokohama City University, Yokohama, Kanagawa, Japan.
authors: Hisashi
authors: H
authors: Hirano
authors: Yokohama City University Hospital, Department of Obstetrics and Gynecology, Yokohama, Kanagawa, Japan.
authors: Etsuko
authors: E
authors: Miyagi
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000097:blood* / Q000175:diagnosis* / Q000601:surgery; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D018394:CA-125 Antigen / Q000097:blood; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D005831:Genital Diseases, Female / Q000097:blood / Q000175:diagnosis; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D008597:Menstrual Cycle; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000175:diagnosis* / Q000601:surgery; D010051:Ovarian Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000601:surgery; D057234:Preoperative Period; D011379:Prognosis; D012372:ROC Curve; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D006023:Glycoproteins; C021240:tissue-factor-pathway inhibitor 2