Fiche publication
Date publication
septembre 2021
Journal
Life science alliance
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAUMERT Thomas
,
Dr LINDNER Véronique
,
Pr PESSAUX Patrick
,
Dr CROUCHET Emilie
,
Dr VERRIER Eloi
Tous les auteurs :
Jühling F, Saviano A, Ponsolles C, Heydmann L, Crouchet E, Durand SC, El Saghire H, Felli E, Lindner V, Pessaux P, Pochet N, Schuster C, Verrier ER, Baumert TF
Lien Pubmed
Résumé
Chronic hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC) world-wide. The molecular mechanisms of viral hepatocarcinogenesis are still partially understood. Here, we applied two complementary single-cell RNA-sequencing protocols to investigate HBV-HCC host cell interactions at the single cell level of patient-derived HCC. Computational analyses revealed a marked HCC heterogeneity with a robust and significant correlation between HBV reads and cancer cell differentiation. Viral reads significantly correlated with the expression of HBV-dependency factors such as in different tumor compartments. Analyses of virus-induced host responses identified previously undiscovered pathways mediating viral carcinogenesis, such as E2F- and MYC targets as well as adipogenesis. Mapping of fused HBV-host cell transcripts allowed the characterization of integration sites in individual cancer cells. Collectively, single-cell RNA-Seq unravels heterogeneity and compartmentalization of both, virus and cancer identifying new candidate pathways for viral hepatocarcinogenesis. The perturbation of pro-carcinogenic gene expression even at low HBV levels highlights the need of HBV cure to eliminate HCC risk.
Référence
Life Sci Alliance. 2021 Sep;4(9):
