Comparison of hepatic and serum lipid signatures in hepatocellular carcinoma patients leads to the discovery of diagnostic and prognostic biomarkers
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Yonghai Lu1,2,*, Juanjuan Chen3,*, Chong Huang4, Ning Li4, Li Zou1, Sin Eng Chia1, Shengsen Chen4, Kangkang Yu4, Qingxia Ling4, Qi Cheng4, Mengqi Zhu4, Weidong Zhang5, Mingquan Chen4 and Choon Nam Ong1,6
1Saw Swee Hock School of Public Health, National University of Singapore, Singapore
2Institute of Nutrition and Health, Qingdao University, Qingdao, Shandong, China
3School of Marine Science, Ningbo University, Ningbo, Zhejiang, China
4Department of Infectious Diseases and Hepatology of Huashan Hospital, Fudan University, Shanghai, China
5School of Pharmacy, Second Military Medical University, Shanghai, China
6NUS Environmental Research Institute, National University of Singapore, Singapore
*These authors contributed equally to this work
Choon Nam Ong, email: [email protected]
Mingquan Chen, email: [email protected]
Keywords: lipidomics, mass spectrometry, hepatocellular carcinoma, liver tissue, serum
Received: June 22, 2017 Accepted: September 03, 2017 Published: December 13, 2017
We compared hepatic and serum lipid changes in hepatocellular carcinoma (HCC) patients to have a better understanding of the molecular pathogenesis of this disease and discovery novel lipid biomarkers. Hepatic and serum lipid profiling was conducted in paired liver and serum samples from 50 HCC patients and 24 healthy controls. A total of 20 hepatic and 40 serum lipid signatures were identified, yet there was hardly any significant correlation between them. The results indicated that triglycerides and phosphatidylcholines contributed significantly to altered hepatic lipids, whereas triglycerides and phosphatidylethanolamine-based plasmalogens (PEp) contributed most to altered serum lipids. In serum, PEp (36:4) and (40:6) showed a fair capability to discriminate HCC patients from healthy controls, and were significantly associated with HCC tumor grades (p < 0.05), and thus were identified as potential diagnostic and prognostic biomarkers of HCC. These findings were confirmed by a validation study conducted in an independent cohort consisting of 18 HCC, 20 cirrhosis patients, and 20 healthy controls. This study suggests that hepatic and serum lipid signatures of HCC have to be considered as mostly independent, and the results imply potential roles of PEp species, particularly PEp (36:4) and (40:6), as serum biomarkers for HCC diagnosis and progression.
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