CD44 upregulation in chronic liver disease marks the transition to hepatocellular carcinoma and portends poor prognosis
Menée à l'aide de modèles murins et de données cliniques et transcriptomiques de la base "GEO" portant sur des tissus hépatiques normaux, fibrosés, cirrhotiques ou cancéreux, cette étude met en évidence, dans les maladies hépatiques chroniques, une association entre la surexpression du CD44 sur les hépatocytes et la transformation maligne de ces cellules
Background : Hepatocellular carcinoma (HCC) often arises from chronic liver disease, but early biomarkers of malignant transformation are lacking. CD44, a transmembrane glycoprotein with multiple isoforms, has been implicated in cancer progression and immune modulation.
Methods : We analysed CD44 expression in mouse models of chronic and acute liver injury and assessed its clinical relevance in human HCC using bulk and single-cell transcriptomic datasets.
Results : CD44 and its isoforms v6 and v10 were progressively upregulated in chronic liver injury, peaking in HCC. CD44-positive hepatocytes increased with fibrosis severity and were abundant in murine liver tumours. In human HCC, CD44 expression was significantly elevated compared to non-tumorous liver and was associated with reduced overall survival. CD44high tumours showed enrichment in oncogenic signalling pathways and greater infiltration of immunosuppressive cells, including M2 macrophages and Th2 cells. Single-cell RNA-seq confirmed CD44 expression in both tumour and immune cells, linking it to a protumor immune microenvironment.
Conclusions : CD44 is a promising early biomarker of hepatocarcinogenesis and a potential therapeutic target. Its expression reflects disease progression from fibrosis to cancer and is associated with poor prognosis and immune evasion in HCC.
British Journal of Cancer , article en libre accès, 2025