Plasma proteomic analysis reveals altered protein abundances in HIV/HBV co-infection individuals with HCC and with liver cirrhosis

Abstract To develop a risk prediction model for hepatocellular carcinoma (HCC) by screening differentially expressed proteins (DEPs) in HIV/HBV coinfected patients with HCC and liver cirrhosis using proteomic techniques. DEPs were identified in plasma from HIV/HBV co-infected patients with HCC and l...

Full description

Saved in:
Bibliographic Details
Main Authors: Yongxi Zhang, Ping Xu, Xingxia Yu, Ke Zhuang, Xien Gui, Rongrong Yang
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Scientific Reports
Subjects:
Online Access:https://doi.org/10.1038/s41598-025-99072-y
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849728295795425280
author Yongxi Zhang
Ping Xu
Xingxia Yu
Ke Zhuang
Xien Gui
Rongrong Yang
author_facet Yongxi Zhang
Ping Xu
Xingxia Yu
Ke Zhuang
Xien Gui
Rongrong Yang
author_sort Yongxi Zhang
collection DOAJ
description Abstract To develop a risk prediction model for hepatocellular carcinoma (HCC) by screening differentially expressed proteins (DEPs) in HIV/HBV coinfected patients with HCC and liver cirrhosis using proteomic techniques. DEPs were identified in plasma from HIV/HBV co-infected patients with HCC and liver cirrhosis using quantitative liquid chromatography-mass spectrometry (LC-MS). Mapping discovered proteins to the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Disease Ontology (DO) databases yielded annotation information for DEPs. Differential plasma apolipoprotein A-1(APOA1) and transthyretin (TTR) expression levels were validated in 88 HIV/HBV co-infected individuals with HCC and liver cirrhosis. In total, 150 DEPs were discovered. The GO entries were primarily enriched for cutaneous immunological response mediated by circulating immunoglobulin and complement activation, as well as lipoprotein particle. The KEGG pathway enrichment was dominated by complement and coagulation cascades. Six of the 15 items enriched in the DO entries were related to lipid metabolism. APOA1, TTR, Prothrombin (F2), Antithrombin-III (SERPINC1), Alpha-2-HS-glycoprotein (AHSG), Alpha-2-macroglobulin (A2M) and Haptoglobin-related protein (HPR) were finally identified as hub proteins. Finally, a visual logistic model using immunoglobulin heavy variable 3–13 (IGHV3-13) and A2M to predict HCC were constructed. Significant variations in plasma APOA1 and TTR levels were found in HIV/HBV co-infected patients with HCC and liver cirrhosis. The screened hub proteins from DEPs can be employed as possible markers for early HCC detection. The developed HCC prediction model can be used to assess the risk of HCC in HIV/HBV co-infected cirrhotic individuals.
format Article
id doaj-art-1f0787f5e2bc4912a66e1420cb75ba9c
institution DOAJ
issn 2045-2322
language English
publishDate 2025-05-01
publisher Nature Portfolio
record_format Article
series Scientific Reports
spelling doaj-art-1f0787f5e2bc4912a66e1420cb75ba9c2025-08-20T03:09:35ZengNature PortfolioScientific Reports2045-23222025-05-0115111410.1038/s41598-025-99072-yPlasma proteomic analysis reveals altered protein abundances in HIV/HBV co-infection individuals with HCC and with liver cirrhosisYongxi Zhang0Ping Xu1Xingxia Yu2Ke Zhuang3Xien Gui4Rongrong Yang5Department of Infectious Diseases, Zhongnan Hospital of Wuhan UniversityDepartment of Infectious Diseases, Zhongnan Hospital of Wuhan UniversityDepartment of Emergency, Renmin Hospital of Wuhan UniversityABSL-III Laboratory at the Center for Animal Experiment, State Key Laboratory of Virology, Wuhan UniversityDepartment of Infectious Diseases, Zhongnan Hospital of Wuhan UniversityDepartment of Infectious Diseases, Zhongnan Hospital of Wuhan UniversityAbstract To develop a risk prediction model for hepatocellular carcinoma (HCC) by screening differentially expressed proteins (DEPs) in HIV/HBV coinfected patients with HCC and liver cirrhosis using proteomic techniques. DEPs were identified in plasma from HIV/HBV co-infected patients with HCC and liver cirrhosis using quantitative liquid chromatography-mass spectrometry (LC-MS). Mapping discovered proteins to the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Disease Ontology (DO) databases yielded annotation information for DEPs. Differential plasma apolipoprotein A-1(APOA1) and transthyretin (TTR) expression levels were validated in 88 HIV/HBV co-infected individuals with HCC and liver cirrhosis. In total, 150 DEPs were discovered. The GO entries were primarily enriched for cutaneous immunological response mediated by circulating immunoglobulin and complement activation, as well as lipoprotein particle. The KEGG pathway enrichment was dominated by complement and coagulation cascades. Six of the 15 items enriched in the DO entries were related to lipid metabolism. APOA1, TTR, Prothrombin (F2), Antithrombin-III (SERPINC1), Alpha-2-HS-glycoprotein (AHSG), Alpha-2-macroglobulin (A2M) and Haptoglobin-related protein (HPR) were finally identified as hub proteins. Finally, a visual logistic model using immunoglobulin heavy variable 3–13 (IGHV3-13) and A2M to predict HCC were constructed. Significant variations in plasma APOA1 and TTR levels were found in HIV/HBV co-infected patients with HCC and liver cirrhosis. The screened hub proteins from DEPs can be employed as possible markers for early HCC detection. The developed HCC prediction model can be used to assess the risk of HCC in HIV/HBV co-infected cirrhotic individuals.https://doi.org/10.1038/s41598-025-99072-yLiver cirrhosisHepatocellular carcinomaHuman immunodeficiency virusLipid metabolismApolipoprotein A-1Transthyretin
spellingShingle Yongxi Zhang
Ping Xu
Xingxia Yu
Ke Zhuang
Xien Gui
Rongrong Yang
Plasma proteomic analysis reveals altered protein abundances in HIV/HBV co-infection individuals with HCC and with liver cirrhosis
Scientific Reports
Liver cirrhosis
Hepatocellular carcinoma
Human immunodeficiency virus
Lipid metabolism
Apolipoprotein A-1
Transthyretin
title Plasma proteomic analysis reveals altered protein abundances in HIV/HBV co-infection individuals with HCC and with liver cirrhosis
title_full Plasma proteomic analysis reveals altered protein abundances in HIV/HBV co-infection individuals with HCC and with liver cirrhosis
title_fullStr Plasma proteomic analysis reveals altered protein abundances in HIV/HBV co-infection individuals with HCC and with liver cirrhosis
title_full_unstemmed Plasma proteomic analysis reveals altered protein abundances in HIV/HBV co-infection individuals with HCC and with liver cirrhosis
title_short Plasma proteomic analysis reveals altered protein abundances in HIV/HBV co-infection individuals with HCC and with liver cirrhosis
title_sort plasma proteomic analysis reveals altered protein abundances in hiv hbv co infection individuals with hcc and with liver cirrhosis
topic Liver cirrhosis
Hepatocellular carcinoma
Human immunodeficiency virus
Lipid metabolism
Apolipoprotein A-1
Transthyretin
url https://doi.org/10.1038/s41598-025-99072-y
work_keys_str_mv AT yongxizhang plasmaproteomicanalysisrevealsalteredproteinabundancesinhivhbvcoinfectionindividualswithhccandwithlivercirrhosis
AT pingxu plasmaproteomicanalysisrevealsalteredproteinabundancesinhivhbvcoinfectionindividualswithhccandwithlivercirrhosis
AT xingxiayu plasmaproteomicanalysisrevealsalteredproteinabundancesinhivhbvcoinfectionindividualswithhccandwithlivercirrhosis
AT kezhuang plasmaproteomicanalysisrevealsalteredproteinabundancesinhivhbvcoinfectionindividualswithhccandwithlivercirrhosis
AT xiengui plasmaproteomicanalysisrevealsalteredproteinabundancesinhivhbvcoinfectionindividualswithhccandwithlivercirrhosis
AT rongrongyang plasmaproteomicanalysisrevealsalteredproteinabundancesinhivhbvcoinfectionindividualswithhccandwithlivercirrhosis