Classification of the LC4 Primarily-like Cell Line—Recapitulating a CDK4 Overexpressing Immune Evasive HIV-HCV-Induced HCC

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BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality. HCC is characterized by high heterogeneity and, subsequently, adaptation by developing resistance to current treatments. Applying individualized models is crucial to understanding the potential of approved therapies. Therefore, we classify a primary-like cell line derived from the core region of an HCC with underlying HIV-HCV co-infection employing deep analysis on the pathway regulation level. METHODS: We employed DEG analysis, followed by pathway analysis, to characterize the preservation level of the LC4 cells and the level of adoption. Next, we classify the new model for HCC research by employing healthy donor samples, commonly used HCC cell lines, and global RNAseq datasets. RESULTS: LC4 cells reflect the characteristics of the parental cancer region, including immunosuppression and metabolic reprogramming, characterized by the downregulation of drug-metabolizing enzymes compared to healthy individuals, indicating a transition to alternate metabolic pathways. Moreover, we identified specific biomarkers equally regulated in the parental tissue, in global datasets of the same entities as well as in LC4 cells. CONCLUSIONS: We classified LC4 cells as an individual immunosuppressive and highly progressive primary-like HCC cell line. LC4 cells are applicable as a model for preclinical drug testing, minimizing the lack of preclinical models in HCV-HIV-induced HCC research.

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