Metabolomics and network analysis uncovered profound inflammation-associated alterations in hepatitis B virus-related cirrhosis patients with early hepatocellular carcinoma
Zhiyong Du,
Shengju Yin,
Bing Liu,
Wenxin Zhang,
Jiaxu Sun,
Meng Fang,
Yisheng Xu,
Kun Hua,
Pengfei Tu,
Guoliang Zhang,
Ying Ma,
Yingyuan Lu
Affiliations
Zhiyong Du
Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, 100029, China
Shengju Yin
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China; Shanghai Key Laboratory of Children's Environment Health, School of Public Health/Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Shandong Jiaotong Hospital, Jinan, 250031, China
Bing Liu
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China
Wenxin Zhang
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China
Jiaxu Sun
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China
Meng Fang
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China
Yisheng Xu
Waters Technologies Ltd., Beijing, 102600, China
Kun Hua
Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, 100029, China
Pengfei Tu
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China
Guoliang Zhang
School of Basic Medical Sciences, Peking University, Beijing, 100191, China; Corresponding author.
Ying Ma
State Key Laboratory Breeding Base of Dao-di Herbs, National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China; Corresponding author.
Yingyuan Lu
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China; Corresponding author.
Patients with hepatitis B virus (HBV)-related liver cirrhosis (LC) are at high risk for hepatocellular carcinoma (HCC). Limitations in the early detection of HCC give rise to poor survival in this high-risk population. Here, we performed comprehensive metabolomics on health individuals and HBV-related LC patients with and without early HCC. Compared to non-HCC patients (N = 108) and health controls (N = 80), we found that patients with early HCC (N = 224) exhibited a specific plasma metabolome map dominated by lipid alterations, including lysophosphatidylcholines, lysophosphatidic acids and bile acids. Pathway and function network analyses indicated that these metabolite alterations were closely associated with inflammation responses. Using multivariate regression and machine learning approaches, we identified a five-metabolite combination that showed significant performances in differentiating early-HCC from non-HCC than α-fetoprotein (area under the curve values, 0.981 versus 0.613). At metabolomic levels, this work provides additional insights of metabolic dysfunction related to HCC progressions and demonstrates the plasma metabolites might be measured to identify early HCC in patients with HBV-related LC.
