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

Abstract

OBJECTIVE(S): Recurrence of HCC frequently occurs within the first year after hepatectomy probably due to circulating cancer cells that shed from the primary tumor prior to hepatectomy. Since cancer stem cells (CSCs) are more likely to initiate tumor growth than mature cancer cells, a high level of circulating CSCs may be a hint for HCC recurrence. This study aims to investigate whether circulating CSCs can predict recurrence of HCC after hepatectomy. METHODS: Multi-color flow cytometry was used to detect the number of circulating CSCs (CD45-CD90+CD44+) in the peripheral circulation of 82 patients of HCC one day before hepatectomy. The patients were monitored by CT or MRI for recurrence every three months. RESULTS: Forty-one (50%) patients had recurrence after a median follow-up period of 17.5 months (range 2.7–64.9 months). The patients with recurrence had a higher median level of circulating CSCs than those without recurrence (0.02% vs. 0.01%, p < 0.0001). Circulating CSCs >/=0.01% predicted intrahepatic recurrences (relative risk 3.54, 95% C.I. 1.41–8.88) and extrahepatic recurrences (relative risk 10.15, 95% C.I. 3–34.4). Patients with >0.01% circulating CSCs had a lower two-year disease-free rate (22.7% vs. 64.2%, p < 0.0001) and overall survival rate (58.5% vs. 94.1%, p = 0.0005) than those with </=0.01% circulating CSCs. On multivariate analysis, circulating CSCs >0.01%, tumor stage and tumor size were independent factors affecting the disease-free survival. CONCLUSIONS: Circulating CSCs predicted post-hepatectomy recurrence of HCC with high accuracy. Circulating CSCs may be the target of eradication in the prevention of metastasis of HCC after hepatectomy.