AUTHOR=Bi Huaqiang , Feng Kai , Wang Xiaofei , Zheng Ping , Qu Chengming , Ma Kuansheng 

TITLE=Transcriptomic and metabolomic analysis of peri-tumoral hepatic tissue in hepatocellular carcinoma: unveiling the molecular landscape of immune checkpoint therapy resistance

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1304996

DOI=10.3389/fphar.2023.1304996

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Hepatocellular carcinoma (HCC) often resists traditional treatments, necessitating new therapeutic approaches. With immune checkpoint therapy emerging as a promising alternative, understanding its resistance mechanisms becomes crucial.</p><p><bold>Methods:</bold> Using 22 samples from 11 HCC patients, we conducted a comprehensive transcriptomic and metabolomic analysis of peri-tumoral hepatic tissues from those treated with Atezolizumab.</p><p><bold>Results:</bold> We identified significant metabolic alterations and a correlation between the COMMD3-BMI1 gene and Dephospho-CoA metabolite. Findings suggest these as potential markers for therapeutic resistance, as evidenced by upregulated COMMD3-BMI1 and downregulated Dephospho-CoA in non-responsive patients, with animal models further supporting these observations.</p><p><bold>Discussion:</bold> The study highlights COMMD3-BMI1 and Dephospho-CoA as critical actors in immune checkpoint therapy resistance in HCC, providing insights and potential pathways for more effective therapeutic strategies.</p>