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. 2017 Dec 13;9(4):5032-5043.
doi: 10.18632/oncotarget.23494. eCollection 2018 Jan 12.

Comparison of hepatic and serum lipid signatures in hepatocellular carcinoma patients leads to the discovery of diagnostic and prognostic biomarkers

Yonghai Lu #  1   2 , Juanjuan Chen #  3 , Chong Huang  4 , Ning Li  4 , Li Zou  1 , Sin Eng Chia  1 , Shengsen Chen  4 , Kangkang Yu  4 , Qingxia Ling  4 , Qi Cheng  4 , Mengqi Zhu  4 , Weidong Zhang  5 , Mingquan Chen  4 , Choon Nam Ong  1   6
Affiliations

Comparison of hepatic and serum lipid signatures in hepatocellular carcinoma patients leads to the discovery of diagnostic and prognostic biomarkers

Yonghai Lu et al. Oncotarget. .

Abstract

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.

Keywords: hepatocellular carcinoma; lipidomics; liver tissue; mass spectrometry; serum.

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Conflict of interest statement

CONFLICTS OF INTEREST The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
OPLS-DA score scatter plots show perturbations of hepatic (A) and serum (B) lipid profiles in hepatocellular carcinoma (HCC) patients.
Figure 2
Figure 2. Diagnostic capabilities of PEp (36:4) and (40:6) for hepatocellular carcinoma (HCC)
(A) Altered expressions of PEp (36:4) and (40:6) in serum of healthy subjects, early-stage HCC patients, and late-stage HCC patients; (B) ROC curve of serum PEp (36:4) and (40:6) in the discovery set; (C) Altered expressions of PEp (36:4) and (40:6) in serum of healthy subjects, liver cirrhosis patients, and HCC patients; (D) ROC curve of the combination of PEp (36:4) and (40:6) in the validation set; (E) Discrimination of healthy subjects, liver cirrhosis patients, and HCC patients by using the combined serum levels of PEp (36:4) and (40:6), at a cut-off of probability of 0.5; (F) Diagnostic accuracy of the combined marker PEp (36:4) and (40:6) for HCC patients with different concentrations of AFP in the validation set.
See this image and copyright information in PMC

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