Serum Proteomic Changes as Candidate Biomarkers of Intermediate Liver Fibrosis in Chronic Hepatitis B Infection
Serum Proteomic Changes as Candidate Biomarkers of Intermediate Liver Fibrosis in Chronic Hepatitis B Infection
复制标题
血清蛋白质组变化作为慢性乙型肝炎感染中度肝纤维化的候选生物标志物
DOI：
10.1089/omi.2018.0179
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发表时间：
2019-03-01
影响因子：
3.3
通讯作者：
Huang, Hai-Jun
中科院分区：
文献类型：
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作者：
Dai, Yi-Ning;Tu, Yue-Xing;Huang, Hai-Jun
慢性乙型肝炎(CHB)是全球主要的健康负担。肝纤维化是慢性乙型肝炎的主要组织病理学改变，如不及时治疗，可能导致终末期肝病，是一种潜伏的过程。中期肝纤维化(S2)是开始抗病毒治疗的最佳时机。本研究的目的是检测慢性乙肝患者不同纤维化阶段的蛋白质组学变化，以期确定未来S2的血清生物标志物。90例慢性乙型肝炎患者分为轻度肝纤维化(S0-1)、中度肝纤维化(S2)和重度肝纤维化(S3-4)，其中男性61例，女性29例，年龄25-63岁。应用等压标记进行相对和绝对定量，以筛选在患者组之间差异表达的蛋白质。另外46名慢性乙型肝炎患者(年龄25-59岁，31名男性和15名女性)和16名健康对照组(26-61岁，11名男性和5名女性)进入验证组。用酶联免疫吸附试验验证候选生物标志物的诊断价值。我们发现139个蛋白质在不同的纤维化阶段配对比较中差异表达。选择5个候选蛋白作为S2的潜在生物标志物进行进一步验证。值得注意的是，无花果蛋白-2(FCN2)和羧基肽酶B2(CPB2)在患者和健康对照组中的表达存在差异。综上所述，本文报道的血清蛋白质组学变化为未来识别慢性乙型病毒性肝炎肝纤维化阶段的生物标志物候选研究提供了新的分子线索。特别是，FCN2和CPB2需要进一步研究它们在CHB发病机制中的可能作用。
Chronic hepatitis B (CHB) is a major global health burden. Liver fibrosis, an insidious process, is the main histopathological change in CHB that might lead to the end-stage liver disease if left untreated. The intermediate liver fibrosis (S2) is the optimal time to start antiviral therapy. The aim of the present study was to examine the proteomic changes in patients with CHB at different fibrotic stages, with a view to identify future serum biomarkers for S2. Ninety CHB patients were grouped into mild (S0-1), intermediate (S2), and severe liver fibrosis (S3-4) (61 men and 29 women; age 25-63 years). Isobaric tagging for relative and absolute quantitation was applied to screen proteins differentially expressed among the patient groups. Another 46 patients with CHB (age 25-59 years; 31 men and 15 women), and 16 healthy controls (age 26-61 years; 11 men and 5 women) were enrolled in a validation group. Enzyme-linked immunosorbent assay was used to verify the diagnostic value of the candidate biomarkers. We found 139 proteins that were differentially expressed between various fibrotic stage-paired comparisons. Five protein candidates were selected as potential biomarkers of S2 for further verification. Notably, ficolin-2 (FCN2) and carboxypeptidase B2 (CPB2) showed differential expression between patients and healthy controls. In conclusion, serum proteomic changes reported here offer new molecular leads for future research on biomarker candidates to identify liver fibrotic stages in CHB. In particular, FCN2 and CPB2 warrant further research on their possible mechanistic involvement in CHB pathogenesis.