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Gynecol Oncol. 2015 Dec;139(3):520-8. doi: 10.1016/j.ygyno.2015.10.012. Epub 2015 Oct 18.

Fully-sialylated alpha-chain of complement 4-binding protein: Diagnostic utility for ovarian clear cell carcinoma.

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Department of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa 2591193, Japan. Electronic address:
Advanced Technology Center, Medical Solution Segment, LSI Medience Corporation, Tokyo 1748555, Japan.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles 90033, USA.
Department of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa 2591193, Japan.
Mitsubishi Chemical Group Science and Technology Research Center, Inc., Yokohama 2278502, Japan.
Department of Obstetrics and Gynecology, Sho Hospital, Tokyo 1730004, Japan.
International Sales Department, LSI Medience Corporation, Tokyo 1018517, Japan.



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.


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).


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.


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.


Complement 4-binding protein; Endometrioma: early detection; Full sialylation; Ovarian clear cell carcinoma

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