Measurement of Circulating Tumor Cells Determines Treatment Response and Exitus in Patients with Hepatocellular Carcinoma Submitted to Transarterial Chemoembolization

Abstract

Circulating tumor cells (CTCs) enumeration is a promising technique to predict cancer prognosis and treatment response. CTCs were evaluated in healthy subjects, cirrhotic controls and hepatocarcinoma (HCC) patients. CTCs were isolated using microfluidic system based on the expression of EpCAM, EGFR and three epithelial to mesenchymal transition (EMT) markers. Patients were stratified according to disease progression and exitus. Although counts of individual CTCs, clustered CTCs and α-fetoprotein (AFP) at basal level in patients with HCC were significantly increased compared with the values obtained in cirrhotic patients and control subjects, only individual CTCs (p=0.027), but not clustered CTCs (p=0.063) and AFP (p=0.072), were independent predictors of HCC development. The univariate regression model showed that basal levels of CTCs46 were related to high risk of HCC (Odds Ratio 3.467, p=0.011). The stratification of our cohort according to disease progression and death showed that basal individual CTCs 76 (Hazard Ratio 5.131, p=0.004) were related to disease progression, as well as the difference of clustered CTCs between 1-month and baseline levels 1.5 were related to death (Hazard Ratio 10.204, p=0.036). In conclusion, the preoperative and 1-month measurements of CTCs in blood constitute useful markers to predict the outcome of patients under TACE treatment.