Qin Gang, Wang Bo, Zhang Geng, Wu Lili, Zhu Peng, Zhang Qian
Department of Gastroenterology, Suining First People's Hospital, Suining, People's Republic of China.
Department of Infectious Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, People's Republic of China.
Infect Drug Resist. 2023 Aug 31;16:5765-5775. doi: 10.2147/IDR.S417472. eCollection 2023.
To screen out potential prognostic biomarkers for HBV-related acute-on-chronic liver failure (HBV-ACLF).
Peripheral blood samples of HBV-ACLF patients (n=56) and normal controls (n=15) from the Affiliated Hospital of Southwest Medical University from January 2021 to April 2022 were collected, 5 normal patients and 10 patients with ACLF were randomly selected for Data independent acquisition (DIA) mass spectrometry analysis, and the potential core proteins were screened out via bioinformatics. All samples were validated by Enzyme linked immunosorbent assays (ELISA) technology, and the survival curve was constructed based on the patient's 90-day survival time.
A total of 247 differentially expressed proteins (DEPs) were screened, of which 148 were upregulated and 99 were down-regulated. The DEPs were mainly enriched in high-density lipoprotein particle remodeling, coagulation, and hemostasis and participated in signaling pathways such as cholesterol metabolism, coagulation cascades, and PPAR signaling pathway. Finally, bikunin was selected for further study and validated via the ELISA, compared with the normal group, bikunin was poorly expressed in the HBV-ACLF group, the difference was statistically significant (P < 0.0001), the area under the curve (AUC) for Receiver operating characteristic (ROC) analysis was 0.917. Furthermore, compared with the non-survival group, bikunin was highly expressed in the HBV-ACLF survival group, the difference was statistically significant (P=0.0015), and the survival curve showed a positive correlation with patient survival (P=0.0063).
The level of plasma bikunin in HBV-ACLF is down-regulated, which is positively correlated with the survival of the patients with HBV-ACLF, and is expected to become a new prognostic biomarker.
筛选出乙型肝炎病毒相关慢加急性肝衰竭（HBV-ACLF）潜在的预后生物标志物。
收集2021年1月至2022年4月西南医科大学附属医院HBV-ACLF患者（n=56）和正常对照者（n=15）的外周血样本，随机选取5例正常患者和10例ACLF患者进行数据非依赖采集（DIA）质谱分析，通过生物信息学筛选潜在的核心蛋白。所有样本采用酶联免疫吸附测定（ELISA）技术进行验证，并根据患者90天生存时间构建生存曲线。
共筛选出247个差异表达蛋白（DEP），其中148个上调，99个下调。这些DEP主要富集于高密度脂蛋白颗粒重塑、凝血和止血过程，并参与胆固醇代谢、凝血级联反应和PPAR信号通路等信号通路。最后，选择 bikunin 进行进一步研究，并通过 ELISA 验证，与正常组相比，bikunin 在 HBV-ACLF 组中表达较低，差异有统计学意义（P<0.0001），受试者工作特征（ROC）分析的曲线下面积（AUC）为0.917。此外，与非生存组相比，bikunin 在 HBV-ACLF 生存组中高表达，差异有统计学意义（P=0.0015），生存曲线显示与患者生存呈正相关（P=0.0063）。
HBV-ACLF患者血浆bikunin水平下调，与HBV-ACLF患者生存呈正相关，有望成为新的预后生物标志物。
