LAUSR

Introduction: The association between cholesteryl ester (CE) profiles in the liver and oncogenesis, gender, and age disparities in hepatocellular carcinoma (HCC) has not been studied to date. This study aims to compare CE profiles between benign liver tissue (BLT) and HCC, and to correlate these findings with oncogenesis and disparities in patients with HCC. Methods: Paired BLT and HCC samples obtained from 32 patients with the diagnosis of HCC were used for lipid extraction. Electrospray ionized mass spectrometry (ESI-MS) was used to determine CE profiles, including 22 individual CE species and the total levels of CE. The CE profiles in BLT and HCC were compared and stratified between subgroups based on the gender and age of the patients. The student T-test was used for statistical analysis and the significant p-value was set at 0.05. Results: Total CE levels were higher in HCC than in BLT, but not statistically significant (1.8-fold, p=0.16). Interestingly, 5 saturated CE individual species and 2 mono-unsaturated individual CE species (C14:0, C16:0, C16:1, C18:0, C18:1, C19:0, and C20:0) were significantly higher in HCC than in BLT (2.4 to 14-fold higher). None of the individual poly-unsaturated CE species showed a statistical difference between HCC and BLT. In males, the levels of 3 saturated individual CE species (C16.0, 16:0, and C20:0) were significantly higher in HCC than in BLT (1.9 to 21.3-fold higher levels). In contrast, CE 16:1 was significantly lower in HCC than in BLT (0.9-fold, p=0.02) in males. In females, none of the CE profiles showed a significant difference between HCC and BLT. Total CE levels were 2.1-fold higher in males with HCC than in females with HCC (18.6nM vs. 8.92nM). In young patients (<66-year-old), individual CE species C14:0 was significantly higher in HCC than in BLT (19.1-fold, p=0.038). In old patients (≥66-year old), individual CE species C20:0 was significantly higher in HCC than in BLT. Total CE levels were 2.1-fold higher in young HCC patients than in old HCC patients (13.68nM vs. 6.45nM). Conclusion: This study reveals that an increase in hepatic total CE levels and individual CE species are associated with the oncogenesis of HCC and show gender and age disparities. These findings could be helpful in prevention, treatment, exploring biomarkers, and understanding disparities in HCC. Citation Format: Nazar Rahmanov, Zhirong Liu, Jinghe Mao, Patrick Kyle, Xinchun Zhou. The significance of cholesteryl ester profiles in hepatocellular carcinoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3706.