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Biomed Chromatogr. 2018 May;32(5):e4180. doi: 10.1002/bmc.4180. Epub 2018 Jan 23.

UPLC-MS/MS based diagnostics for epithelial ovarian cancer using fully sialylated C4-binding protein.

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Medical Solution Promotion Department, Medical Solution Segment, LSI Medience Corporation, Tokyo, Japan.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA.
Department of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa, Japan.
Department of Obstetrics and Gynecology, Sho Hospital, Tokyo, Japan.


Serum levels of fully sialylated C4-binding protein (FS-C4BP) are remarkably elevated in patients with epithelial ovarian cancer (EOC) and can be used as a marker to distinguish ovarian clear cell carcinoma from endometrioma. This study aimed to develop a stable, robust and reliable liquid chromatography-hybrid mass spectrometry (UPLC-MS/MS) based diagnostic method that would generalize FS-C4BP as a clinical EOC biomarker. Glycopeptides derived from 20 μL of trypsin-digested serum glycoprotein were analyzed via UPLC equipped with an electrospray ionization time-of-flight mass spectrometer. This UPLC-MS/MS-based diagnostic method was optimized for FS-C4BP and validated using sera from 119 patients with EOC and 127 women without cancer. A1958 (C4BP peptide with two fully sialylated biantennary glycans) was selected as a marker of FS-C4BP because its level in serum was highest among FS-C4BP family members. Preparation and UPLC-MS/MS were optimized for A1958, and performance and robustness were significantly improved relative to our previous method. An area under the curve analysis of the FS-C4BP index receiver operating characteristic curve revealed that the ratio between A1958 and A1813 (C4BP peptide with two partially sialylated biantennary glycans) reached 85%. A combination of the FS-C4BP index and carbohydrate antigen-125 levels further enhanced the sensitivity and specificity.


UPLC-MS/MS; biomarker; clear cell carcinoma; complement 4-binding protein; ovarian cancer

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