👤 Keiko Ozato

Hepatocellular carcinoma (HCC) arises from various etiologies, including viral hepatitis and non-viral liver diseases. Although comprehensive genomic profiling (CGP) is increasingly applied in oncology, the influence of disease etiology on the genomic landscape of HCC and biomarker applicability remains insufficiently characterized. CGP data from 551 patients with HCC, registered in the National Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, were analyzed after excluding cases with undefined etiology. We characterized the mutational landscape, compared mutation frequencies among HBV-, HCV-, and non-viral, non-cholestatic (nBnC)-related HCC, assessed the association between homologous recombination repair (HRR)-related gene alterations and tumor mutation burden (TMB), and evaluated the detection rates of actionable mutations in tissue- versus liquid-based CGP. Telomerase reverse transcriptase splice site mutations were the most common genomic alteration and were consistently observed across all etiologic groups. Although mutations in AXIN1 and DDR2 genes showed modest enrichment in HCV- and HBV-related HCC, respectively, the overall mutational profiles remained largely conserved across etiologies. TMB was significantly lower in nBnC-HCC compared to HCV-related HCC but showed no association with HRR-related mutations. The detection rates of targetable mutations were similar between tissue and liquid biopsies; however, only a small proportion of patients received matched therapies. Real-world data indicate a conserved genomic architecture in HCC regardless of etiology, supporting unified therapeutic approaches. The absence of a relationship between HRR alterations and TMB suggests distinct biological mechanisms. Liquid biopsy remains a reliable option when tissues are unavailable in managing patients with HCC. Show less

We investigated mRNA expression of 49 nuclear hormone receptors (NRs) and 35 transcriptional coregulators in mouse bone marrow-derived dendritic cells (DCs) upon infection with Newcastle Disease virus (NDV) or murine cytomegalovirus (MCMV). These viruses regulated mRNA expression of some NRs among which NOR1 and LXRα were highly induced at mRNA and protein levels. Exogenous expression of the latter NRs repressed IRF3- or IRF7-induced transactivation of the interferon β promoter and NDV infection further potentiated their repressive effect. The viral infection also significantly regulated mRNA expression of some coregulators, including HDAC1. Toll-like receptor ligands regulated NR and coregulator mRNA expression similar to the viruses. Thus, NRs and coregulators are integral components of DC-organizing anti-viral response wherein NOR1 and LXRα participate in regulating interferon production. Show less