Abstract 1348: Investigation of sex disparity in hepatocarcinogenesis using a hydrodynamic tail vein injection mouse model

Abstract The incidence of hepatocellular carcinoma (HCC), the major form of liver cancer, is two to three times higher in men than in women. Understanding the gender disparity in HCC incidence is challenging due to HCC development being multifactorial, including variations in risk factors, behaviors, and hormones. The liver is a sexually dimorphic organ, and estrogen has been proven to have a protective effect against the development of HCC, although the mechanism is not fully understood. We used the hydrodynamic tail vein injection (HTVI) mouse model of HCC to investigate potential mechanisms underlying the sex disparity of HCC incidence. This model eliminates social and behavioral aspects of gender disparity and allows us to determine if there is biological sex disparity and what role estrogen and androgens play in tumor development. In our preliminary study, the expression vectors of oncogenes, ΔN90-β-catenin and c-MET, to be integrated into the hepatocyte genome via transposons, were co-injected with a Sleeping Beauty (SB) transposase to induce HCC in FVB/NJ mice. Based on plasma alpha-fetoprotein (AFP), an HCC blood biomarker, male FVB/NJ mice had a significantly higher mean AFP trend in comparison to females, indicating that the males developed liver tumors at a faster rate than females. ΔN90-β-catenin and c-MET gene copy number were confirmed to be equally transfected and integrated in both male and female FVB/NJ tumors by quantitative PCR (qPCR). The expression of ΔN90-β-catenin and c-MET transgenes was also shown to be similar between male and female mouse HCC tumors by RT-qPCR and RNA-seq. We plan to repeat the HTVI of ΔN90-β-cat, c-MET, and SB to validate that the males will develop liver tumors at a faster rate than female mice. We will also Western Blot to determine if there is sex disparity in the abundance of the transfected oncogene proteins. In addition, we will compare the abundance of various types of immune cells present in the tumor immune microenvironment (TIME) to interpret potential sex-dependent immune cell differences in the tumor liver. Our research has the potential to uncover mechanisms underlying the sex-dependent disparity in HCC development and progression and the contribution of immune cells to the sex disparity. Citation Format: Araceli Selena Bernal, Morgana McLaughlin, Ankur Tiwari, Brittany Barre, Francisco Cigarroa, LuZhe Sun. Investigation of sex disparity in hepatocarcinogenesis using a hydrodynamic tail vein injection mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1348.