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Abstract：
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.
摘要：
慢性乙型肝炎（CHB）是全球主要的健康负担。肝纤维化,一个阴险的过程，是CHB的主要组织病理学变化，如果不及时治疗，可能导致终末期肝病。中间肝纤维化（S2）是开始抗病毒治疗的最佳时间。本研究的目的是检查不同纤维化阶段CHB患者的蛋白质组学变化，以期确定S2的未来血清生物标志物。90例CHB患者分组为轻度（S0-1），中间（S2），和严重肝纤维化（S3-4）（61名男性和29名女性;年龄25-63岁）。用于相对和绝对定量的等压标记用于筛选患者组中差异表达的蛋白质。另外46例CHB患者（年龄25-59岁;31名男性和15名女性），16名健康对照(年龄26-61岁;11名男性和5名女性)纳入验证组.酶联免疫吸附试验用于验证候选生物标志物的诊断价值。我们发现了139种蛋白质在各种纤维化阶段配对比较之间差异表达。选择5种蛋白质候选物作为S2的潜在生物标志物用于进一步验证。值得注意的是,ficolin-2（FCN2）和羧肽酶B2（CPB2）在患者和健康对照组之间显示出差异表达。总之,这里报道的血清蛋白质组变化为未来的生物标志物候选研究提供了新的分子线索，以确定CHB中的肝纤维化阶段。特别是,FCN2和CPB2需要进一步研究其可能的机制参与CHB发病机制。
