Abstract A006: Development of a syngeneic transplant rat model for the identification of an mRNA signature associated with metastatic hepatocellular carcinoma

Abstract

Abstract Approximately 70% of patients with hepatocellular carcinoma (HCC) die of metastasis, mainly in the lung, due in part to late diagnosis. Therefore, in vivo models that are representative of metastatic HCC biology in patients must include factors that are essential for metastasis development, such as an immunocompetent system and a tumor microenvironment with homotypic interactions. This will allow the identification of new prognostic biomarkers for patients with metastatic HCC that are efficient and accessible. We developed two hepatocellular carcinoma cell lines for syngeneic transplant models in immunocompetent rats: Samy (nonmetastatic) and Samy Met (metastatic). These cell lines allow the development of cancer and metastasis in a homotypic environment with a complete immune system; therefore, they are expected to be representative of what happens in patients with metastatic HCC. Both cell lines were biologically characterized, and the primary tumors they produced were used in a comparative transcriptomic study to identify a metastatic HCC molecular signature that may function as a prognostic biomarker. The differentially expressed genes (DEGs) were related to relevant biological processes, such as metastasis, cancer stem cells (CSCs), and tumor growth, and all of these processes are essential for cancer progression. Among the top 50 DEGs, an mRNA firm was assembled, including 3 upregulated genes (ITGB6, SEMA3F, and NDC80) and 7 downregulated genes (COL15A1, ATP13A4, C18ORF26, PRKG2, ITM2A, IGSF9B, and CNTN1). The firm was related to poor survival in patients with HCC and had good accuracy in predicting macrovascular invasion, which is a strong predictor of poor HCC outcome, both after surgical resection and after liver transplantation. Citation Format: Theresa G Azcárraga Acosta, Carolina Piña Vazquéz, Hury V Hernández Galdámez, Karla M Rubio Nava, Josué Guzmán Linares, Ivonne Ramírez Díaz, Guillermo Barreto, Mario A Aguilar Chaparro, Stefan Günther, Saul Villa Treviño, Mireya De la Garza, Teresita del niño Jesús Flores Téllez, Veronica R Vásquez Garzón. Development of a syngeneic transplant rat model for the identification of an mRNA signature associated with metastatic hepatocellular carcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr A006.