PRM-MS Quantitative Analysis of Isomeric N-Glycopeptides Derived from Human Serum Haptoglobin of Patients with Cirrhosis and Hepatocellular Carcinoma.
PRM-MS Quantitative Analysis of Isomeric N-Glycopeptides Derived from Human Serum Haptoglobin of Patients with Cirrhosis and Hepatocellular Carcinoma.
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DOI：
10.3390/metabo11080563
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发表时间：
2021-08-23
期刊：
影响因子：
4.1
通讯作者：
Mechref Y
中科院分区：
文献类型：
--
作者：
Gutierrez Reyes CD;Huang Y;Atashi M;Zhang J;Zhu J;Liu S;Parikh ND;Singal AG;Dai J;Lubman DM;Mechref Y
目前，监测策略对肝硬化和肝细胞癌（HCC）的早期检测性能不足。血清结合珠蛋白的糖基化水平在肝硬化和肝癌之间有显著差异，可用于诊断。我们进行了全面的液相色谱-平行反应监测-质谱（LC-PRM-MS）的方法，其中有针对性的平行反应监测（PRM）策略耦合到一个强大的LC系统，以研究从肝硬化和HCC患者中提取的结合珠蛋白（Hp）的位点特异性异构。我们发现，我们的策略是能够确定大量的异构N-糖肽，主要位于Hp糖基化位点Asn 207。发现四种N-糖肽在肝硬化和HCC样品之间的丰度有显著变化（p < 0.05）。重要的N-糖肽与甲胎蛋白（AFP）或其自身的策略组合，可以更好地估计其各自的受试者工作特征（ROC）曲线相对于AFP的曲线下面积（AUC）。AFP与异构体唾液酸化岩藻糖基化N-糖肽Asn 207 + 5-6-1-2和Asn 207 + 5-6-1-3的组合导致AUC值为0.98，而AFP单独的AUC值为0.85。当比较肝硬化与早期HCC时，异构体N-糖肽Asn 207 + 5-6-0-1更好地估计关于AFP的AUC（分别为AUCAFP = 0.81和AUCAsn 207 + 5-6-0-1 = 0.88）。
Currently, surveillance strategies have inadequate performance for cirrhosis and early detection of hepatocellular carcinoma (HCC). The glycosylation of serum haptoglobin has shown to have significant differences between cirrhosis and HCC, thus can be used for diagnosis. We performed a comprehensive liquid chromatography—parallel reaction monitoring—mass spectrometry (LC-PRM-MS) approach, where a targeted parallel reaction monitoring (PRM) strategy was coupled to a powerful LC system, to study the site-specific isomerism of haptoglobin (Hp) extracted from cirrhosis and HCC patients. We found that our strategy was able to identify a large number of isomeric N-glycopeptides, mainly located in the Hp glycosylation site Asn207. Four N-glycopeptides were found to have significant changes in abundance between cirrhosis and HCC samples (p < 0.05). Strategic combinations of the significant N-glycopeptides, either with alpha-fetoprotein (AFP) or themselves, better estimate the areas under the curve (AUC) of their respective receiver operating characteristic (ROC) curves with respect to AFP. The combination of AFP with the isomeric sialylated fucosylated N-glycopeptides Asn207 + 5-6-1-2 and Asn207 + 5-6-1-3, resulted with an AUC value of 0.98, while the AUC value for AFP alone was 0.85. When comparing cirrhosis vs. early HCC, the isomeric N-glycopeptide Asn207 + 5-6-0-1 better estimated AUC with respect to AFP (AUCAFP = 0.81, and AUCAsn207 + 5-6-0-1 = 0.88, respectively).
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影响因子：
4.4
作者：
West CA;Wang M;Herrera H;Liang H;Black A;Angel PM;Drake RR;Mehta AS
通讯作者：
Mehta AS
影响因子：
29.4
作者：
Tzartzeva K;Obi J;Rich NE;Parikh ND;Marrero JA;Yopp A;Waljee AK;Singal AG
通讯作者：
Singal AG
影响因子：
12.6
作者：
Best, Jan;Bechmann, Lars P.;Canbay, Ali
通讯作者：
Canbay, Ali
影响因子：
7.4
作者：
Mysling, Simon;Palmisano, Giuseppe;Thaysen-Andersen, Morten
通讯作者：
Thaysen-Andersen, Morten
影响因子：
4.3
作者：
Kim, Kwang Hoe;Park, Gun Wook;Yoo, Jong Shin
通讯作者：
Yoo, Jong Shin