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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.

Author information

1
Medical Solution Promotion Department, Medical Solution Segment, LSI Medience Corporation, Tokyo, Japan.
2
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA.
3
Department of Obstetrics and Gynecology, Tokai University School of Medicine, Kanagawa, Japan.
4
Department of Obstetrics and Gynecology, Sho Hospital, Tokyo, Japan.

Abstract

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.

KEYWORDS:

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

PMID:
29265394
DOI:
10.1002/bmc.4180
[Indexed for MEDLINE]

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