Glycopeptides with Sialyl Lewis Antigen in Serum Haptoglobin as Candidate Biomarkers for Nonalcoholic Steatohepatitis Hepatocellular Carcinoma Using a Higher-Energy Collision-Induced Dissociation Parallel Reaction Monitoring-Mass Spectrometry Method.
Glycopeptides with Sialyl Lewis Antigen in Serum Haptoglobin as Candidate Biomarkers for Nonalcoholic Steatohepatitis Hepatocellular Carcinoma Using a Higher-Energy Collision-Induced Dissociation Parallel Reaction Monitoring-Mass Spectrometry Method.
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DOI：
10.1021/acsomega.2c02600
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发表时间：
2022-07-05
期刊：
影响因子：
4.1
通讯作者：
中科院分区：
文献类型：
--
作者：
非酒精性脂肪性肝炎(NASH)是美国肝细胞癌(HCC)增长最快的原因。血清蛋白特定糖位上N-糖基化的变化已被研究为早期发现NASH相关肝癌的潜在标记物。在这里，我们报道了一种来源于血清结合珠蛋白(HP)的唾液酸路易斯结构的糖肽，作为NASH相关肝癌的潜在标记物，在95例NASH患者中，包括46例肝硬化，32例早期肝癌和17例晚期肝癌。用LC-HCD-PRM-MS/MS对患者血清中的Hp免疫分离物进行分析，然后用Skyline软件进行数据分析。2个位于N184位的糖肽和4个位于N241位的糖肽在肝细胞癌与非酒精性肝硬化组之间存在显著差异(P<；0.05)。N-糖肽N241_A4G4F2S4与甲胎蛋白(α-FetoProtein，AFP)联合检测肝癌的效果最佳，其曲线下面积估计值(AUC值)为0.898(95%CI：0.835，0.951)，而单独使用AFP的AUC值为0.790(95%CI值，0.697，0.872)(P=0.048)。在90%的特异度下，N241_A4G4F2S4+AFP联合检测的敏感性为63.3%，而单独使用AFP的敏感性为52.3%。当使用三个标记时，AFP+N241_A2G2F1S2+N241_A4G4F2S4组合的AUC值估计为0.928(95%CI：0.877，0.970)。提示N241_A4G4F2S4可能在肝细胞癌与非酒精性肝硬变的鉴别诊断中起重要作用。
Nonalcoholic steatohepatitis (NASH) is the fastest growing cause of hepatocellular carcinoma (HCC) in the United States. Changes in N-glycosylation on specific glycosites of serum proteins have been investigated as potential markers for the early detection of NASH-related HCC. Herein, we report a glycopeptide with a Sialyl Lewis structure derived from serum haptoglobin (Hp) as a potential marker for NASH related HCCs among 95 patients with NASH, including 46 cirrhosis, 32 early-stage HCC, and 17 late-stage HCC. Hp immuno-isolated from patient serum was analyzed using LC-HCD-PRM-MS/MS followed by data analysis via Skyline software. Two glycopeptides involving site N184 and four glycopeptides involving site N241 were significantly changed in patients with HCC vs NASH cirrhosis (P < 0.05). The two-marker panel using N-glycopeptide N241_A4G4F2S4 showed the best performance for HCC detection when combined with α-fetoprotein (AFP), with an improved estimated area under the curve (AUC) = 0.898 (95% CI: 0.835, 0.951), compared to the AUC of 0.790(95% CI, 0.697 0.872) using AFP alone (P = 0.048). At 90% specificity, the combination of N241_A4G4F2S4 + AFP had an improved sensitivity of 63.3%, compared to the sensitivity of 52.3% using AFP alone. When using three markers, the panel of AFP + N241_A2G2F1S2 + N241_A4G4F2S4 yielded an estimated AUC of 0.928 (95% CI: 0.877, 0.970). Our findings indicated that N241_A4G4F2S4 may play an important role in distinguishing HCC from NASH cirrhosis.
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影响因子：
7.6
作者：
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影响因子：
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影响因子：
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DOI：
10.6004/jnccn.2018.7105
发表时间：
2019-04-01
影响因子：
13.4
作者：
Hester, Caitlin A.;Rich, Nicole E.;Yopp, Adam C.
通讯作者：
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