Potential lipid species biomarkers for hepatocellular carcinoma

Authors: Leung K, Peart D, Kuang Y

Category: Early Detection & Risk Prediction
Conference Year: 2021

Abstract Body:
Purpose of Study To identify lipid species biomarkers for early detection of hepatocellular carcinoma (HCC) in cirrhosis Methods STAM mouse model was used to investigate the species alteration in lipid metabolism. A total of 30 liver tissue samples were collected from normal mice (C), STAM mice with liver fibrosis (F) and STAM mice with HCC (H). Ten samples from each stage were included. Lipidomics analysis was performed by direct infusion electrospray ionization mass spectrometry (ESI-MS) to detect 1881 lipid species. Lipid species across stages were compared by one-way analysis of variance (ANOVA) followed by Tukey test or Kruskal–Wallis test (KWT) followed by Mann–Whitney U test. Lipid species with significant change (p < 0.05) across stages and significant change in all possible pairwise comparisons (p <0.05) were retained for correlation analysis. Spearman's rank correlations between the lipid species retained at each stage were assessed and compared. Results Results from means comparisons showed a significant decrease in nine lipid species from ether-linked phosphatidylcholine (ePC), phosphatidylcholine (PC) and sphingomyelin (SM) during the progression from normal liver through cirrhosis towards HCC. Among the nine lipid species retained, ePC(40:4) showed significant decrease (p < 0.05) with more than four-fold change from F to H. Spearman's rank correlation analysis indicates that the relationship between SM(16:0) and SM(24:0) is more positive in F (rho= 0.855) than in C (rho= 0.661) while the relationship between SM (16:0) and ePC (38:2) is positive in C (rho= 0.758) and negative in F (rho= -0.636). A more positive relationships between ePC(38:4) and PC(42:3) in C than H and a less positive relationship between ePC(38:4) and ePC (38:2) in C than H were reported with Spearman's rank correlation coefficients increases from 0.745 to 0.867 and decreases from 0.77 to 0.683 respectively. Conclusions Our study showed that PC(34:1), PC(38:1), PC(42:3), SM(16:0), SM(24:0), ePC(38:2), ePC(38:4), ePC(40:4) and ePC(40:5) may serve as biomarkers for early detection of HCC in cirrhosis. Additional study is needed to understand the detailed mechanism, our study provides novel insights in the progress of cirrhosis towards HCC.

Keywords: hepatocellular carcinoma, cirrhosis, lipidomics, biomarker