Evaluation of serum phosphopeptides as potential cancer biomarkers by mass spectrometric absolute quantification

Zhai, Guijin; Wu, Xiaoyan; Luo, Qun; Wu, Kui; Zhao, Yao; Liu, Jianan; Xiong, Shaoxiang; Feng, Yu‐Qi; Yang, Liping; Wang, Fuyi

doi:10.1016/j.talanta.2014.03.025

Cited by 22 publications

(19 citation statements)

References 46 publications

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“…29 However, the application of TiO 2 /MHMSS to capture phosphopeptides was not very satisfactory, perhaps due to the relatively lower efficiency of the TiO 2 /MHMSS materials for capturing the phosphopeptides in sera. Recently, Feng et al have shown that zirconium arsenatemodied magnetic nanoparticles (ZrAs-Fe 3 O 4 @SiO 2 ) had high selectivity for phosphopeptides and excellent capture capability towards multiply-phosphopeptides.…”

Section: Resultsmentioning

confidence: 99%

“…The four serum phosphopeptides, which were commonly identied in serum 29,32 and generated from brinogen A, 33 are chemically synthesized with and without incorporation of deuterated glycine residues as ideal external standards to gain multi-point standard calibration curves. The synthetic deuterium-labeled phosphopeptides of which the sequences match exactly to endogenous peptides are added to serum as internal standards before samples processing, which signicantly improves the accuracy of the quantication of phosphopeptides.…”

mentioning

confidence: 99%

“…29 To further evaluate the potential of serum phosphopeptides as biomarkers for GC, we applied the proposed method described above to determine the concentration of phosphopeptides in serum samples collected from 30 healthy people and 60 GC patients. Table S2 † summarizes the demographic data (ages and sex) for patients and healthy controls both overall and separately for the training set (TS) and validating set (VS).…”

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confidence: 99%

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Evaluation of serum phosphopeptides as potential biomarkers of gastric cancer

et al. 2017

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Gastric cancer (GC) is the fourth most commonly diagnosed cancer and the third leading cause of cancerrelated deaths. Most GC deaths can be prevented by early diagnosis. However, biomarkers with high sensitivity and specificity are rare. Comprehensive serum phosphopeptides analysis may lead to the discovery of novel biomarkers for GC. In this work, we report a mass spectrometric strategy for the evaluation of serum phosphopeptides separated and enriched by ZrAs-Fe 3 O 4 @SiO 2 nanoparticles. Four endogenous phosphopeptides in sera generated by degradation of fibrinogen were synthesized with light-and heavy-glycine residues, respectively, as external/internal standards, and used to gain multipoint standard calibration curves for absolute quantification of phosphopeptides by LC-ESI-MS following ZrAs-Fe 3 O 4 @SiO 2 enrichment. The ESI-MS signal ratios of the four pairs of light-/heavy-phosphopeptide standards captured by ZrAs-Fe 3 O 4 @SiO 2 from aqueous solutions are linearly correlated with the molar ratios of the "light" to "heavy" phosphopeptides over the range of 0.05-5 mM with an r 2 of up to 0.998 and a slope of close to 1. The recovery of the four phosphopeptides spiked at low, medium and high levels in human sera were 94.7-107.5% with RSDs in the range of 0.6-8.2%. The validated method was utilized to measure the phosphopeptide levels of serum samples from 30 healthy persons and 60 GC patients. Receiver operating characteristic (ROC) analysis shows that one phosphopeptide (F3:DpSGEGDFLAEGGGVR) yields high sensitivity and specificity of 90.0% and 96.7%, respectively, in the validation set for discriminating GC patients from healthy controls. Overall, 53 of 60 GC cases and 29 of 30 controls were correctly classified, including eight of nine GC patients at stage I. These results suggest that F3 in sera may be a potential biomarker for GC diagnosis, particularly for early stage cases.

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Evaluation of serum phosphopeptides as potential biomarkers of gastric cancer

et al. 2017

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“…This method was successful in determining the binding ratio of ruthenium anticancer complexes to Cys15, Cys48, Met92 and Cys102 in GST‐π. However, when the NAS isotopic labelling occurred only at the N‐terminal, the mass difference between light and heavy peptides was only 3 Da, where the isotopic signals may overlap, so a correction based on the isotopic ratios of the peptide pair was required for accurate quantification . Moreover, as the NAS labelling is applied to terminal amines and amines of lysine in the side chain, the primary MS‐based quantification cannot distinguish the exact binding sites at the single residue level if there is more than one binding site in a metallated peptide.…”

Section: Discussionmentioning

confidence: 99%

Mass spectrometric quantification of the binding ratio of metal‐based anticancer complexes with protein thiols

Han

Guo

Zheng

et al. 2019

Rapid Comm Mass Spectrometry

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Rationale The binding ratio of metal complexes with cysteinyl thiols in proteins plays an important role in deciphering the mechanisms of action of therapeutic metal complexes, but its analysis is still a significant challenge. In this work, a quantitative mass spectrometry method is developed to determine the binding ratio of metal‐based anticancer complexes with cysteines in human copper chaperone protein Atox1. Methods A novel strategy based on a thiol‐specific stable isotopic labelling reagent was developed to determine the binding ratio of metal‐based anticancer complexes, namely cisplatin and organometallic ruthenium complex [(η6‐biphenyl)RuCl(en)]PF6 (en = ethylenediamine), with the cysteinyl residues of Atox1. Results Both cisplatin and the ruthenium complex were reactive not only to Cys15 and/or Cys18, the copper(I) binding site of Atox1, but also to Cys44. The binding ratios of the ruthenium complex with the cysteinyl residues were much higher than those of cisplatin. However, the addition of copper(I) could markedly increase the binding ratios of cysteinyl residues of Atox1 with cisplatin, but not with the ruthenium complex. Conclusions This strategy can not only precisely determine the binding ratios of metal complexes to protein thiols, but also be helpful in distinguishing thiol‐binding sites from other binding sites of metal complexes in proteins. We expect wide application of this method to the research of covalent/coordinative interactions between metal complexes and protein thiols.

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“…S14b †), validating the credibility of relative quantification in this range. So far, abnormal expression of serum fibrinogen and its phosphorylated fragments has been discovered and discussed in the cases of ovarian cancer, 55 gastric cancer 56 and liver cancer. 28 Unlike solid cancer tumors, leukemia is a group of hematologic malignancies featured by a large number of abnormal white blood cells, toward which phosphoproteomic research was extensively carried out regarding its complicated subtypes.…”

Section: Relative Quantification Of Serum Phosphopeptidesmentioning

confidence: 99%

Weaving a two-dimensional fishing net from titanoniobate nanosheets embedded with Fe₃O₄nanocrystals for highly efficient capture and isotope labeling of phosphopeptides

et al. 2015

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Qualitative and quantitative characterization of phosphopeptides by means of mass spectrometry (MS) is the main goal of MS-based phosphoproteomics, but suffers from their low abundance in the large haystack of various biological molecules. Herein, we introduce two-dimensional (2D) metal oxides to tackle this biological separation issue. A nanocomposite composed of titanoniobate nanosheets embedded with Fe₃O₄ nanocrystals (Fe₃O₄-TiNbNS) is constructed via a facile cation-exchange approach, and adopted for the capture and isotope labeling of phosphopeptides. In this nanoarchitecture, the 2D titanoniobate nanosheets offer enlarged surface area and a spacious microenvironment for capturing phosphopeptides, while the Fe₃O₄ nanocrystals not only incorporate a magnetic response into the composite but, more importantly, also disrupt the restacking process between the titanoniobate nanosheets and thus preserve a greater specific surface for binding phosphopeptides. Owing to the extended active surface, abundant Lewis acid sites and excellent magnetic controllability, Fe₃O₄-TiNbNS demonstrates superior sensitivity, selectivity and capacity over homogeneous bulk metal oxides, layered oxides, and even restacked nanosheets in phosphopeptide enrichment, and further allows in situ isotope labeling to quantify aberrantly-regulated phosphopeptides from sera of leukemia patients. This composite nanosheet greatly contributes to the MS analysis of phosphopeptides and gives inspiration in the pursuit of 2D structured materials for separation of other biological molecules of interests.

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Evaluation of serum phosphopeptides as potential cancer biomarkers by mass spectrometric absolute quantification

Cited by 22 publications

References 46 publications

Evaluation of serum phosphopeptides as potential biomarkers of gastric cancer

Evaluation of serum phosphopeptides as potential biomarkers of gastric cancer

Mass spectrometric quantification of the binding ratio of metal‐based anticancer complexes with protein thiols

Weaving a two-dimensional fishing net from titanoniobate nanosheets embedded with Fe₃O₄nanocrystals for highly efficient capture and isotope labeling of phosphopeptides

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Evaluation of serum phosphopeptides as potential cancer biomarkers by mass spectrometric absolute quantification

Cited by 22 publications

References 46 publications

Evaluation of serum phosphopeptides as potential biomarkers of gastric cancer

Evaluation of serum phosphopeptides as potential biomarkers of gastric cancer

Mass spectrometric quantification of the binding ratio of metal‐based anticancer complexes with protein thiols

Weaving a two-dimensional fishing net from titanoniobate nanosheets embedded with Fe3O4nanocrystals for highly efficient capture and isotope labeling of phosphopeptides

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Weaving a two-dimensional fishing net from titanoniobate nanosheets embedded with Fe₃O₄nanocrystals for highly efficient capture and isotope labeling of phosphopeptides