Abstract

Abstract Purpose of Study To investigate alterations in lipid metabolism during carcinogenesis from pretumor tissue towards hepatocellular carcinoma (HCC) and to identify lipid species biomarkers for early detection of HCC. Methods Liver tissue samples were collected from HCC patients. The samples were used to investigate the differences in lipid compositions between tumor and its surrounding hepatic tissue (SHT). A sample of the liver tumor and a sample of SHT were collected from each patient. A total of 32 samples were included in this study. Lipid profiling was performed using an automated electrospray ionization–tandem mass spectrometry with continuous infusion at 30 μl/min. The signal detection limit is 0.0005 mol. Concentrations of 1881 lipid species in tissue samples were analyzed. These lipid species include 348 species in 13 polar lipid groups, 44 species in triacylglycerol (TAG) group and 1489 species containing specific fatty acyl (FA). Lipid species with signal detected above or equal to the detection limit and coefficient of variation below 0.3 were retained for statistical analysis. Concentration differences in lipid species between HCC and SHT were compared using paired t-test or Wilcox signed rank. Differences in lipid compositions between HCC and SHT were assessed. Results Our study shows that significant difference (p < 0.05) of lipid species between SHT and HCC was found in 61 species including 50 species from polar lipid groups and 11 species from TAG group. Most of these species are phosphatidylcholine, ether-linked phosphatidylcholine and TAG species accounted for 36.07%, 13.11% and 18.03% respectively. In addition, significant changes in total ether-linked phosphatidylethanolamine (ePE) and total phosphatidylinositol (PI) were observed. Furthermore, there were significant decreases in FA 18:2 and FA18:3, but significant increase in FA 18:0 in HCC compared with that in SHT. Conclusions Our study suggests that total ePE, total PI, FA 18:0, FA 18:2 and FA 18:3 may serve as biomarkers for the early detection of HCC. Additional study is needed to understand the detailed mechanism of lipid alteration. Our study provides novel insights in the progress of pretumor tissue towards HCC. Citation Format: Kit Yee Leung, KayLee Freitas, Yu Kuang. Identification of lipid species: potential biomarkers for early detection of hepatocellular carcinoma [abstract]. In: Proceedings of the AACR Special Conference: Advances in the Pathogenesis and Molecular Therapies of Liver Cancer; 2022 May 5-8; Boston, MA. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(17_Suppl):Abstract nr PO020.

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