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.

CONCLUSION:

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: Mikio Mikami, Kazuhiro Tanabe, Koji Matsuo, Yuko Miyazaki, Masaki Miyazawa, Masaru Hayashi, Satoshi Asai, Masae Ikeda, Masako Shida, Takeshi Hirasawa, Nozomi Kojima, Ryuichiro Sho, Sadayo Iijima
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 139 Issue 3 Pg. 520-8 (Dec 2015) ISSN: 1095-6859 [Electronic] United States
• PMID: 26477941 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers, Tumor
• C4BPA protein, human
• CA-125 Antigen
• Complement C4b-Binding Protein
• Glycopeptides

Topics

• Adenocarcinoma, Clear Cell (blood, pathology)
• Adult
• Aged
• Area Under Curve
• Biomarkers, Tumor (chemistry, metabolism)
• CA-125 Antigen (blood)
• Case-Control Studies
• Chromatography, Liquid
• Complement C4b-Binding Protein (chemistry, metabolism)
• Endometriosis (blood)
• Female
• Glycopeptides (blood)
• Humans
• Mass Spectrometry
• Middle Aged
• Neoplasm Staging
• Ovarian Neoplasms (blood, pathology)
• Predictive Value of Tests
• ROC Curve