基于LC / MS的血清生物标志物全球代谢组学鉴定，可将肝细胞

StephenW

LC/MS-Based Global Metabolomic Identification of Serum Biomarkers Differentiating Hepatocellular Carcinoma from Chronic Hepatitis B and Liver Cirrhosis
Hong Y Pan  1 , Qing Q Wu  1   2 , Qiao Q Yin  1   3 , Yi N Dai  1 , Yi C Huang  1 , Wei Zheng  1 , Tian C Hui  1   3 , Mei J Chen  1 , Ming S Wang  1 , Jia J Zhang  1 , Hai J Huang  1 , Yong X Tong  1
Affiliations
Affiliations

    1
    Department of Infectious Diseases, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, No. 158 Shangtang Road, Hangzhou, Zhejiang 310014, China.
    2
    The Second Clinical Medical College, Zhejiang Chinese Medical University, No. 548 Binwen Road, Hangzhou, Zhejiang 310053, China.
    3
    Bengbu Medical College, No. 2600 Donghai Road, Bengbu, Anhui 233030, China.

    PMID: 33490775 PMCID: PMC7818305 DOI: 10.1021/acsomega.0c04259

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Abstract

Chronic hepatitis B virus (CHB) infection is one of the primary risk factors associated with the development of hepatocellular carcinoma (HCC). Despite having been extensively studied, diagnosing early-stage HCC remains challenging, and diagnosed patients have a poor (3-5%) survival rate. Identifying new approaches to detect changes in the serum metabolic profiles of patients with CHB and liver cirrhosis (LC) may provide a valuable approach to better detect HCC at an early stage when it is still amenable to treatment, thereby improving patient prognosis and survival. In the present study, we, therefore, employed a liquid chromatography-mass spectrometry (LC-MS)-based approach to evaluate the serum metabolic profiles of 30 CHB patients, 29 LC patients, and 30 HCC patients. We then employed appropriate statistical methods to identify those metabolites that were best able to distinguish HCC cases from LC and CHB controls. A mass-based database was then used to putatively identify these metabolites. We then confirmed the identities of a subset of these metabolites through comparisons with the MS/MS fragmentation patterns and retention times of reference standards. The serum samples were then reanalyzed to quantify the levels of these selected metabolites and of other metabolites that have previously been identified as potential HCC biomarkers. Through this approach, we observed clear differences in the metabolite profiles of the CHB, LC, and HCC patient groups in both positive- and negative-ion modes. We found that the levels of taurodeoxy cholic acid (TCA) and 1,2-diacyl-3-β-d-galactosyl-sn-glycerol rose with the progression from CHB to LC to HCC, whereas levels of 5-hydroxy-6E,8Z,11Z,14Z,17Z-eicosapentaenoic acid, and glycyrrhizic acid were gradually reduced with liver disease progression in these groups. The ROC analysis showed that taurodeoxy cholic acid (TCA), 1,2-diacyl-3-β-d-galactosyl-sn-glycerol, 5-hydroxy-6E,8Z,11Z,14Z,17Z-eicosapentaenoic acid, and glycyrrhizic acid had a diagnosis performance with liver disease progression. These four metabolites have a significant correlation with alpha fetal protein (AFP) level and age. Our results highlight novel metabolic biomarkers that have the potential to be used for differentiating between CHB, LC, and HCC patients, thereby facilitating the identification and treatment of patients with early-stage HCC.

© 2021 American Chemical Society.

StephenW

基于LC / MS的血清生物标志物全球代谢组学鉴定，可将肝细胞癌与慢性乙型肝炎和肝硬化区别开来
洪彦潘1，青奇武1 2，乔奇音1 3，艺黛1，艺Yi黄1，卫政1，田Tian辉1 3，梅静辰1，王明声1，张佳J 1，黄海J 1，雍X童1
隶属关系
隶属关系

    1个
    浙江省人民医院传染病科，杭州医学院附属人民医院，浙江杭州上塘路158号310014
    2
    浙江中医药大学第二临床医学院，浙江杭州杭州滨文路548号310053
    3
    蚌埠医学院，安徽蚌埠东海路2600号233030

    PMID：33490775 PMCID：PMC7818305 DOI：10.1021 / acsomega.0c04259

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抽象

慢性乙型肝炎病毒（CHB）感染是与肝细胞癌（HCC）发生相关的主要危险因素之一。尽管已进行了广泛研究，但诊断早期HCC仍具有挑战性，并且诊断出的患者生存率较低（3-5％）。鉴定出可检测CHB和肝硬化（LC）患者血清代谢谱变化的新方法，可能会提供一种有价值的方法，以便在仍可接受治疗的早期阶段更好地检测HCC，从而改善患者的预后和生存率。因此，在本研究中，我们采用了基于液相色谱-质谱（LC-MS）的方法来评估30例CHB患者，29例LC患者和30例HCC患者的血清代谢谱。然后，我们采用适当的统计方法来鉴定那些最能区分HCC病例与LC和CHB对照的代谢物。然后使用基于质量的数据库来推定鉴定这些代谢物。然后，通过与MS / MS碎片图谱和参考标准品的保留时间进行比较，我们确认了这些代谢物的一部分。然后重新分析血清样品，以量化这些选定代谢物和先前已被鉴定为潜在HCC生物标志物的其他代谢物的水平。通过这种方法，我们观察到在正离子和负离子模式下，CHB，LC和HCC患者组的代谢物谱存在明显差异。我们发现，牛磺脱氧胆酸（TCA）和1,2-二酰基3-β-d-半乳糖基-sn-甘油的水平随着从CHB到LC到HCC的发展而上升，而5-羟基-6E，这些组中，随着肝脏疾病的进展，8Z，11Z，14Z，17Z-二十碳五烯酸和甘草酸逐渐减少。 ROC分析表明，牛磺脱氧胆酸（TCA），1,2-二酰基-3-β-d-半乳糖基-sn-甘油，5-羟基-6E，8Z，11Z，14Z，17Z-二十碳五烯酸和甘草酸具有肝病进展的诊断表现。这四种代谢物与α胎儿蛋白（AFP）的水平和年龄有着显着的相关性。我们的结果突出了新颖的代谢生物标志物，它们有潜力用于区分CHB，LC和HCC患者，从而有助于早期HCC患者的识别和治疗。

©2021美国化学会。

StephenW

https://pubs.acs.org/doi/pdf/10.1021/acsomega.0c04259