Prediction of post-hepatectomy HCC recurrence by circulating cancer stem cells

Abstract

BACKGROUND: Recurrence of HCC frequently occurs within the first year after hepatectomy. Intrahepatic recurrence is due to new tumorogenic foci, whereas extrahepatic recurrence is probably related to circulating tumor cells shed from the primary tumor prior to hepatectomy. Since cancer stem cells (CSCs) are more likely to initiate tumor growth than mature cancer cells, high level of CSCs may be a hint for HCC recurrence. OBJECTIVES: This study aims to investigate whether circulating CSCs can predict recurrence of HCC after hepatectomy. METHODS: Multi-colour flow cytometry was used to detect the number of circulating CSCs (CD45-CD90+CD44+) in the peripheral circulation of 53 patients of HCC one day before curative hepatectomy. The patients were monitored by CT or MRI for recurrence every three months. RESULTS: Twenty-three patients had recurrence (intrahepatic and/or extrahepatic) after a median follow-up period of 20 months (range 2 – 48 months). The patients with recurrence had a higher level of circulating CSCs than those without (0.04% vs. 0%, p = 0.001). Patients with >0.01% circulating CSCs had a higher 2-year recurrence rate (78.2% vs. 24%, p = 0.0001) and a lower 2-year overall survival rate (55% vs. 88.8%, p = 0.0136) than those with ≤0.01% circulating CSCs. Extrahepatic recurrence occurred in the lung (8), bone (2), diaphragm (1), lymph nodes (3), adrenal gland (1) and spleen (2) in 14 patients. Sensitivity, specificity and accuracy of circulating CSCs >0.01% predicting extrahepatic recurrence were 86%, 67% and 72% respectively. Only 2 of 25 patients with circulating CSCs <0.01% developed extrahepatic recurrence, and none of the 15 patients with CSCs undetectable developed extrahepatic recurrence. CONCLUSION: Circulating CSCs predicted post-hepatectomy recurrence of HCC with high accuracy. Circulating CSCs may be the target of eradication in the prevention of extrahepatic metastasis of HCC after hepatectomy. REFERENCES: Yang ZF, Ho DW, Ng MN, et al. Significance of CD90+ Cancer Stem Cells in Human Liver Cancer. Cancer Cell 2008; 13: 153-166.