1 Department of Infectious Diseases, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.
2 Department of Intensive Care Unit, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.
OMICS. 2019 Mar;23(3):167-179. doi: 10.1089/omi.2018.0179.
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.
慢性乙型肝炎（CHB）是全球主要的健康负担之一。肝纤维化是一种隐匿性的过程，是 CHB 的主要组织病理学改变，如果不治疗，可能会导致终末期肝病。中重度肝纤维化（S2）是开始抗病毒治疗的最佳时机。本研究旨在探讨不同纤维化阶段 CHB 患者的蛋白质组学变化，以期发现 S2 的未来血清生物标志物。90 例 CHB 患者分为轻度（S0-1）、中度（S2）和重度肝纤维化（S3-4）（61 名男性和 29 名女性；年龄 25-63 岁）。应用相对和绝对定量同位素标记（iTRAQ）技术筛选出患者组间差异表达的蛋白质。另外，又招募了 46 例 CHB 患者（年龄 25-59 岁；31 名男性和 15 名女性）和 16 例健康对照者（年龄 26-61 岁；11 名男性和 5 名女性）进入验证组。酶联免疫吸附试验（ELISA）用于验证候选生物标志物的诊断价值。我们发现了 139 种在不同纤维化阶段配对比较中差异表达的蛋白质。选择了 5 种蛋白质候选物作为 S2 的潜在生物标志物进行进一步验证。值得注意的是，ficolin-2（FCN2）和羧肽酶 B2（CPB2）在患者和健康对照者之间显示出差异表达。总之，本研究报道的血清蛋白质组学变化为 CHB 肝纤维化阶段的生物标志物候选物的进一步研究提供了新的分子线索。特别是，FCN2 和 CPB2 值得进一步研究它们在 CHB 发病机制中的可能机制作用。
