Stemness CD24 activation promotes hepatocellular carcinoma progression via an immune escape mechanism

Cluster of differentiation 24 (CD24) serves as a liver cancer stem cell marker, and its upregulation is related to chronic liver disease malignancy. However, the exact relationship between CD24 expression and hepatocarcinogenesis remains unknown.

To investigate CD24 levels among individuals with chronic liver diseases and confirm the alterations in CD24 and programmed death-ligand 1 (PD-L1) expression in a dynamic model of rat hepatocarcinogenesis.

Approved by the ethics committee, CD24 levels were detected in the serum of 129 patients with hepatocellular carcinoma (HCC), 72 patients with chronic hepatitis (CH), 60 patients with liver cirrhosis (LC) and 111 normal control (NC). Receiver operating characteristic curves and clinicopathological characteristics of CD24 were used to evaluate the diagnostic or prognostic value for HCC, and the CD24⁺ T lymphocyte ratio and dynamic alterations in CD24 and PD-L1 expression were confirmed in a rat HCC model.

Compared with those in the CH, LC and NC groups, the average CD24 level in the HCC group was significantly greater (P < 0.01). The CD24⁺ T-cell ratio in the HCC group was greater than that in the CH or NC group. Clinicopathological characteristics of high CD24 in HCC patients included hepatitis B virus infection, single/multicenter status, tumor size, lymph node or extrahepatic metastasis, differentiation degree, tumor-node-metastasis grade, Child-Pugh score, portal vein tumor thrombus and poor prognosis. Mechanistically, CD24 is dynamically upregulated during hepatocarcinogenesis and closely positively correlated with PD-L1 for immune escape, metastasis (CD44), and with respect to HCC markers (Wnt3a, GPC-3 and alpha-fetoprotein).

Activated CD24 promoted HCC formation through programmed death-ligand 1 signaling and could be a valuable biomarker for monitoring chronic liver disease malignancy.