Plasma lipidomic analysis reveals disruption of ether phosphatidylcholine biosynthesis and facilitates early detection of hepatitis B-related hepatocellular carcinoma

Abstract Background Hepatocellular carcinoma (HCC) is the third deadliest malignant tumor worldwide. Most patients are initially diagnosed as HCC at advanced stages and are too late for radical treatment by surgery, resulting in poor prognosis. Over 50% of the HCC patients are caused by hepatitis B...

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Main Authors: Yuyao Yuan, Donghao Yin, Xuemeng Yang, Di Liu, Hui Shan, Juan Luo, Xiuhui Li, Yuxin Yin
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Lipids in Health and Disease
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Online Access:https://doi.org/10.1186/s12944-025-02475-z
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author Yuyao Yuan
Donghao Yin
Xuemeng Yang
Di Liu
Hui Shan
Juan Luo
Xiuhui Li
Yuxin Yin
author_facet Yuyao Yuan
Donghao Yin
Xuemeng Yang
Di Liu
Hui Shan
Juan Luo
Xiuhui Li
Yuxin Yin
author_sort Yuyao Yuan
collection DOAJ
description Abstract Background Hepatocellular carcinoma (HCC) is the third deadliest malignant tumor worldwide. Most patients are initially diagnosed as HCC at advanced stages and are too late for radical treatment by surgery, resulting in poor prognosis. Over 50% of the HCC patients are caused by hepatitis B virus (HBV) infection. Therefore, effective early identification of HCC in the high-risk population with HBV infection is crucial for early intervention of HCC. Methods We employed plasma lipidomics to identify critical lipid classes associated with tumorigenesis in the high-risk population with HBV infection. Potential regulatory mechanisms are validated at multi-omic levels. A machine learning algorithm is used for feature selection and diagnostic modelling, and performance of the models is evaluated by ROC curves. Results We unveiled varied profiles of plasma lipid metabolites in a cohort of 57 HBV-related HCC subjects, 57 HBV-related liver cirrhosis (LC) subjects and 61 chronic hepatitis B (CHB) subjects with matched age, sex and HBV status. We identified a correlation of the ether phosphatidylcholine (PC) synthesis with hepatocarcinogenesis in patients with HBV-related liver diseases. The diagnostic models achieved an area under ROC curve (AUC) of 0.849 for discriminating HCC from CHB and an AUC of 0.829 for discriminating HCC from LC. Conclusions We illustrate the role of ether PC in hepatocarcinogenesis upon HBV infection and provide novel effective markers for early detection of HCC in a cohort with HBV infection.
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spelling doaj-art-38b655d1fd264f2fbad07eb37f4f6d682025-08-20T03:03:45ZengBMCLipids in Health and Disease1476-511X2025-02-0124111310.1186/s12944-025-02475-zPlasma lipidomic analysis reveals disruption of ether phosphatidylcholine biosynthesis and facilitates early detection of hepatitis B-related hepatocellular carcinomaYuyao Yuan0Donghao Yin1Xuemeng Yang2Di Liu3Hui Shan4Juan Luo5Xiuhui Li6Yuxin Yin7Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Peking-Tsinghua Center for Life Sciences, Peking University Health Science CenterBeijing Youan Hospital, Capital Medical UniversityBeijing Youan Hospital, Capital Medical UniversityBeijing Youan Hospital, Capital Medical UniversityInstitute of Precision Medicine, Peking University Shenzhen HospitalInstitute of Precision Medicine, Peking University Shenzhen HospitalBeijing Youan Hospital, Capital Medical UniversityInstitute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Peking-Tsinghua Center for Life Sciences, Peking University Health Science CenterAbstract Background Hepatocellular carcinoma (HCC) is the third deadliest malignant tumor worldwide. Most patients are initially diagnosed as HCC at advanced stages and are too late for radical treatment by surgery, resulting in poor prognosis. Over 50% of the HCC patients are caused by hepatitis B virus (HBV) infection. Therefore, effective early identification of HCC in the high-risk population with HBV infection is crucial for early intervention of HCC. Methods We employed plasma lipidomics to identify critical lipid classes associated with tumorigenesis in the high-risk population with HBV infection. Potential regulatory mechanisms are validated at multi-omic levels. A machine learning algorithm is used for feature selection and diagnostic modelling, and performance of the models is evaluated by ROC curves. Results We unveiled varied profiles of plasma lipid metabolites in a cohort of 57 HBV-related HCC subjects, 57 HBV-related liver cirrhosis (LC) subjects and 61 chronic hepatitis B (CHB) subjects with matched age, sex and HBV status. We identified a correlation of the ether phosphatidylcholine (PC) synthesis with hepatocarcinogenesis in patients with HBV-related liver diseases. The diagnostic models achieved an area under ROC curve (AUC) of 0.849 for discriminating HCC from CHB and an AUC of 0.829 for discriminating HCC from LC. Conclusions We illustrate the role of ether PC in hepatocarcinogenesis upon HBV infection and provide novel effective markers for early detection of HCC in a cohort with HBV infection.https://doi.org/10.1186/s12944-025-02475-zHepatitis BHepatocellular carcinomaPlasma lipidomicsEther phosphatidylcholineEarly detectionMachine learning
spellingShingle Yuyao Yuan
Donghao Yin
Xuemeng Yang
Di Liu
Hui Shan
Juan Luo
Xiuhui Li
Yuxin Yin
Plasma lipidomic analysis reveals disruption of ether phosphatidylcholine biosynthesis and facilitates early detection of hepatitis B-related hepatocellular carcinoma
Lipids in Health and Disease
Hepatitis B
Hepatocellular carcinoma
Plasma lipidomics
Ether phosphatidylcholine
Early detection
Machine learning
title Plasma lipidomic analysis reveals disruption of ether phosphatidylcholine biosynthesis and facilitates early detection of hepatitis B-related hepatocellular carcinoma
title_full Plasma lipidomic analysis reveals disruption of ether phosphatidylcholine biosynthesis and facilitates early detection of hepatitis B-related hepatocellular carcinoma
title_fullStr Plasma lipidomic analysis reveals disruption of ether phosphatidylcholine biosynthesis and facilitates early detection of hepatitis B-related hepatocellular carcinoma
title_full_unstemmed Plasma lipidomic analysis reveals disruption of ether phosphatidylcholine biosynthesis and facilitates early detection of hepatitis B-related hepatocellular carcinoma
title_short Plasma lipidomic analysis reveals disruption of ether phosphatidylcholine biosynthesis and facilitates early detection of hepatitis B-related hepatocellular carcinoma
title_sort plasma lipidomic analysis reveals disruption of ether phosphatidylcholine biosynthesis and facilitates early detection of hepatitis b related hepatocellular carcinoma
topic Hepatitis B
Hepatocellular carcinoma
Plasma lipidomics
Ether phosphatidylcholine
Early detection
Machine learning
url https://doi.org/10.1186/s12944-025-02475-z
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