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Download fileStraightforward and Highly Efficient Strategy for Hepatocellular Carcinoma Glycoprotein Biomarker Discovery Using a Nonglycopeptide-Based Mass Spectrometry Pipeline
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posted on 2019-09-09, 19:04 authored by Wei-Qian Cao, Bi-Yun Jiang, Jiang-Ming Huang, Lei Zhang, Ming-Qi Liu, Jun Yao, Meng-Xi Wu, Li-Juan Zhang, Si-Yuan Kong, Yi Wang, Peng-Yuan YangEfficient
detection of aberrant glycoproteins in serum is particularly
important for biomarker discovery. However, direct quantitation of
glycoproteins in serum remains technically challenging because of
the extraordinary complexity of the serum proteome. In the current
work, we proposed a straightforward and highly efficient strategy
by using the nonglycopeptides releasing from the specifically enriched
glycoproteins for targeted glycoprotein quantification. With this
so-called nonglycopeptide-based mass spectrometry (NGP-MS) strategy,
a powerful and nondiscriminatory pipeline for hepatocellular carcinoma
(HCC) glycoprotein biomarker discovery, verification, and validation
has been developed. First, a data set of 234 NGPs was strictly established
for multiple-reaction monitoring (MRM) quantification in serum. Second,
the NGPs enriched from 20 HCC serum mixtures and 20 normal serum mixtures
were labeled with mTRAQ reagents (Δ0 and Δ8, respectively)
to find the differentially expressed glycoproteins in HCC. A total
of 97 glycoprotein candidates were preliminarily screened and submitted
for absolute quantitation with NGP-based stable-isotope-labeled (SID)-MRM
in the individual samples of 38 HCC serum and 24 normal controls.
Finally, 21 glycoproteins were absolutely quantified with high quality.
The diagnostic sensitivity results showed that three glycoproteins,
β-2-glycoprotein 1 (APOH), α-1-acid glycoprotein 2 (ORM2),
and complement C3 (C3), could be used for the discrimination between
HCC patients and healthy people. A novel glycoprotein biomarker panel
[APOH, ORM2, C3, and α-fetoprotein (AFP)] has proven to outperform
AFP, the known HCC serum biomarker, alone, in this study. We believe
that this strategy and the panel of glycoproteins might hold great
clinical value for HCC detection in the future.
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Hepatocellular Carcinoma Glycoprotein Biomarker Discoverynovel glycoprotein biomarker panelα- fetoproteinSIDbiomarker discoveryserum proteomeNGP-based stable-isotope-labeledHCC serum biomarkerglycoprotein biomarker discoveryserum mixturesHCC detection97 glycoprotein candidates234 NGPscomplement C 3APOHsensitivity results21 glycoproteinsAFPNGP-MSNonglycopeptide-Based Mass Spectrometry Pipeline Efficient detection38 HCC serum20 HCC serum mixturesβ-2- glycoprotein 1hepatocellular carcinomaEfficient StrategyORMHCC patientsglycoprotein quantificationmultiple-reaction monitoringMRMnonglycopeptide-based mass spectrometry