丙型肝炎血清蛋白质组学与转录组学的综合分析

Integrative analysis of serum proteomics and transcriptomics in hepatitis C.

作者信息

Wang Jianqiong, Xia Andong, Tang Min, Yang Shengjun, Shen Yandi, Dao Jinhua, Tao Rui, Yue Wei

机构信息

Department of Clinical Laboratory, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, No.157 Jinbi Road, Kunming, Yunnan, China.

Department of Infectious Diseases and Liver Diseases, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, No.157 Jinbi Road, Kunming, Yunnan, China.

出版信息

Virol J. 2025 Mar 13;22(1):73. doi: 10.1186/s12985-025-02690-1.

OBJECT

Hepatitis C is a contagious disease caused by infection with the hepatitis C virus (HCV) through blood and mother-to-child routes. This study intends to characterize the serum molecular features of hepatitis C using proteomics and transcriptomics.

METHODS

Ctrl (normal population), HCV (population with previous HCV infection), and chronic HCV (patients with persistent HCV infection) groups were set up, and the expression profiles of the proteomes and transcriptomes of serum samples were identified using TMT and RNA-seq. Bioinformatics was applied to perform enrichment analysis and PPI network construction of differentially expressed proteins/genes (DEPs/DEGs). RT-qPCR and western blot verified the expression differences of DEPs/DEGs.

RESULTS

Compared to the Ctrl group, the HCV group had 356 DEPs in serum; compared to the HCV group, the chronic HCV group had 381 DEPs in serum. DEPs are predominantly immunoglobulins and exosomal proteins that regulate carbon dioxide transport, initiation of transcription, immune responses, and bacterial and viral infections. HSPA4, HSPD1, COPS5, PSMD2 and TCP1 are key HCV-associated proteins in DEPs. The HCV group had 684 DEGs compared to the Ctrl group, and the chronic HCV group had 350 DEGs compared to the HCV group. DEGs primarily encode the extracellular matrix and regulate wound healing, cellular communication, oxidative stress, cell adhesion, viral infection, and immunity. KIF11, CENPE, TTK, CDC20 and ASPM are HCV-related hub genes in DEGs. Combined analyses revealed interactions between DEPs and DEGs, especially EIF4A3, MNAT1, and UBE2D1. Moreover, the expression patterns of EIF4A3, EIF2B1, MNAT1, SNRNP70, and UBE2D1 in DEPs/DEGs from Ctrl, HCV, and chronic HCV groups were consistent with the sequencing results.

CONCLUSION

EIF4A3, EIF2B1, MNAT1, SNRNP70, and UBE2D1 are involved in the process of HCV infection and pathogenesis, and they may be potential biomarkers for the treatment of patients with hepatitis C.

目的

丙型肝炎是一种由丙型肝炎病毒（HCV）通过血液和母婴途径感染引起的传染病。本研究旨在利用蛋白质组学和转录组学来表征丙型肝炎的血清分子特征。

方法

设立对照组（正常人群）、HCV组（既往有HCV感染的人群）和慢性HCV组（持续HCV感染的患者），使用TMT和RNA-seq鉴定血清样本蛋白质组和转录组的表达谱。应用生物信息学对差异表达蛋白/基因（DEPs/DEGs）进行富集分析和蛋白质-蛋白质相互作用（PPI）网络构建。逆转录-定量聚合酶链反应（RT-qPCR）和蛋白质免疫印迹法验证DEPs/DEGs的表达差异。

结果

与对照组相比，HCV组血清中有356个DEPs；与HCV组相比，慢性HCV组血清中有381个DEPs。DEPs主要是免疫球蛋白和外泌体蛋白，它们调节二氧化碳运输、转录起始、免疫反应以及细菌和病毒感染。热休克蛋白家族A成员4（HSPA4）、热休克蛋白家族D成员1（HSPD1）、COP9信号复合体亚基5（COPS5）、蛋白酶体26S亚基非ATP酶调节亚基2（PSMD2）和TCP1是DEPs中与HCV相关的关键蛋白。与对照组相比，HCV组有684个DEGs，与HCV组相比，慢性HCV组有350个DEGs。DEGs主要编码细胞外基质并调节伤口愈合、细胞通讯、氧化应激、细胞黏附、病毒感染和免疫。驱动蛋白家族成员11（KIF11）、着丝粒蛋白E（CENPE）、TTK蛋白激酶（TTK）、细胞分裂周期蛋白20（CDC20）和异常纺锤体样微管相关蛋白（ASPM）是DEGs中与HCV相关的枢纽基因。联合分析揭示了DEPs和DEGs之间的相互作用，尤其是真核翻译起始因子4A3（EIF4A3）、周期蛋白依赖性激酶7调节亚基1（MNAT1）和泛素结合酶E2D1（UBE2D1）。此外,EIF4A3、真核翻译起始因子2B亚基1（EIF2B1）、MNAT1、小核核糖核蛋白多肽70（SNRNP70）和UBE2D1在对照组、HCV组和慢性HCV组DEPs/DEGs中的表达模式与测序结果一致。