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

Mikami, Mikio; Tanabe, K.; Matsuo, Koji; Miyazawa, Masaki; Hayashi, Makio; Asai, Satoshi; Ikeda, Masato; Shida, M.; Hirasawa, Takeshi; Sho, R.

doi:10.1016/j.ygyno.2016.04.092

Cited by 3 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The majority of studies investigating N-glycan changes during EOC development have been performed using serum, plasma, ascites, and cell lines, with significant changes identified as being associated with oncogenesis, 17,18 staging, 19,20 histological type, 21,22 and metastasis. 23 However, the preparation methods used required large samples of fresh or frozen specimen.…”

Section: Introductionmentioning

confidence: 99%

Mass spectrometric profiling reveals association of N-glycan patterns with epithelial ovarian cancer progression

et al. 2017

View full text Add to dashboard Cite

Aberrant changes of N-glycan modifications on proteins have been linked to various diseases including different cancers, suggesting possible avenue for exploring their etiologies based on N-glycomic analysis. Changes in N-glycan patterns during epithelial ovarian cancer development have so far been investigated mainly using serum, plasma, ascites, and cell lines. However, changes in patterns of N-glycans in tumor tissues during epithelial ovarian cancer progression have remained largely undefined. To investigate whether changes in N-glycan patterns correlate with oncogenesis and progression of epithelial ovarian cancer, we profiled N-glycans from formalin-fixed paraffin-embedded tissue slides using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and quantitatively compared among different pathological grades of epithelial ovarian cancer and healthy controls. Our results show that among the 80 compositions of N-glycan detected, expression levels of high-mannose type were higher in epithelial ovarian cancer samples than that observed in healthy controls, accompanied by reduced levels of hybrid-type glycans. By applying receiver operating characteristic analysis, we show that a combined panel composed of four high-mannose and three fucosylated neutral complex N-glycans allows for good discrimination of epithelial ovarian cancer from healthy controls. Furthermore, using a statistical analysis of variance assay, we found that different N-glycan patterns, including 2 high-mannose-type, 2 fucosylated and sialylated complex structures, and 10 fucosylated neutral complex N-glycans, exhibited specific changes in N-glycan abundance across epithelial ovarian cancer grades. Together, our results provide strong evidence that N-glycomic changes are a strong indicator for epithelial ovarian cancer pathological grades and should provide avenues to identify novel biomarkers for epithelial ovarian cancer diagnosis and monitoring.

show abstract

Section: Introductionmentioning

confidence: 99%

Mass spectrometric profiling reveals association of N-glycan patterns with epithelial ovarian cancer progression

et al. 2017

View full text Add to dashboard Cite

show abstract

“…We aimed to establish a reliable and high-performance diagnostic method for EOC that was based on FS-C4BP, which we previously identified as an EOC marker ( Mikami et al, 2015 ). The simplification of preparation steps and introduction of an MS/MS technique enabled the detection of the C4BP-related glycopeptide, A1958, the diagnostic performance of which was equal to that of A2160 with significantly better throughput.…”

Section: Discussionmentioning

confidence: 99%

“…We previously identified a C4-binding protein with fully sialylated N -glycans (FS-C4BP) as a novel EOC marker ( Mikami etal., 2015 ). FS-C4BP particularly distinguished early-stage ovarian clear cell carcinoma (OCCC) from endometrioma much more reliably than CA-125.…”

Section: Introductionmentioning

confidence: 99%

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

Tanabe¹,

Matsuo

Miyazawa

et al. 2018

Biomedical Chromatography

View full text Add to dashboard Cite

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. peptide with a fully sialylated and fucosylated triantennary glycan and fully sialylated biantennary glycan, exhibited superior sensitivity and specificity as an EOC marker. However, a complicated lectin-based enrichment process is needed to detect A2160, which is present in serum at quite low levels. This prolonged preparation process led not only to a -----------------------------------------------------------------------This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

show abstract

“…A comprehensive analysis of glycoproteins in the serum samples of patients with PDAC using Tandem Mass Tag™ with MS identified C4b-binding protein α-chain (C4BPA) as a novel serum PDAC biomarker (4). C4BPA is reported to be markedly upregulated in patients with clear-cell ovarian cancer (5) and non-small-cell lung cancer (6). This indicated the diagnostic value of serum C4BPA in different cancers.…”

Section: Introductionmentioning

confidence: 99%

Fucosylated C4b‑binding protein α‑chain, a novel serum biomarker that predicts lymph node metastasis in pancreatic ductal adenocarcinoma

et al. 2020

View full text Add to dashboard Cite

C4b-binding protein α-chain (C4BPA) was previously identified as a novel serum biomarker for pancreatic ductal adenocarcinoma (PDAC). To apply this biomarker for clinical diagnosis, a lectin ELISA was established to measure serum fucosylated (Fuc)-C4BPA levels in 45 patients with PDAC, 20 patients with chronic pancreatitis (CP) and 50 healthy volunteers (HVs) in one training and three validation sets. The lecithin ELISA developed in the current study exhibited satisfactory within-run (2.6–6.7%) and between-day (1.8–3.6%) coefficient of variations. Serum Fuc-C4BPA levels in patients with PDAC (0.54±0.27 AU/ml) was significantly higher than that in HVs (0.21±0.06 AU/ml; P<0.0001) and patients with CP (0.25±0.03 AU/ml; P<0.0001). Additionally, serum Fuc-C4BPA levels in preoperative patients were significantly decreased compared with postoperative patient sera (P<0.0003). The receiver operating characteristic (ROC) curve analyses revealed that the area under the curve (AUC) of Fuc-C4BPA (0.985) was higher than that of carbohydrate antigen (CA)19-9 (0.843), carcinoembryonic antigen (0.548) and total C4BPA (0.875) (P<0.001). To analyze the clinical significance of Fuc-C4BPA, the ability of Fuc-C4BPA to predict lymph node metastasis was compared with that of CA19-9. The AUC of serum Fuc-C4BPA levels (0.703) was significantly higher than that of serum CA19-9 levels (0.500) in patients with PDAC (P<0.001). The current study established a novel lectin ELISA for measuring serum Fuc-C4BPA levels. Thus, Fuc-C4BPA has potential clinical applications owing to its high diagnostic value in PDAC.

show abstract

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

Cited by 3 publications

References 0 publications

Mass spectrometric profiling reveals association of N-glycan patterns with epithelial ovarian cancer progression

Mass spectrometric profiling reveals association of N-glycan patterns with epithelial ovarian cancer progression

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

Fucosylated C4b‑binding protein α‑chain, a novel serum biomarker that predicts lymph node metastasis in pancreatic ductal adenocarcinoma

Contact Info

Product

Resources

About