Association of preoperative EpCAM Circulating Tumor Cells and peripheral Treg cell levels with early recurrence of hepatocellular carcinoma following radical hepatic resection.

This study was carried out to determine the prognostic significance of preoperative peripheral epithelial cell adhesion molecule- positive (EpCAM (+)) circulating tumor cell (CTC) and T regulatory (Treg) cell levels in hepatocellular carcinoma (HCC) patients for the prediction of postoperative recurrence following curative resection. A total of 49 patients about to undergo curative resection for HCC were recruited into the study. PCR and FACS were used to detect the preoperative levels of EpCAM (mRNA+) CTCs and CD4(+)CD25(+)Foxp3(+) Treg cells. The prognostic value of EpCAM (mRNA+) CTCs, CD4(+)CD25(+)Foxp3(+) Treg cells, and other clinicopathological factors were analyzed by applying the Kaplan-Meier method and the multivariate Cox proportional hazards model. The number of EpCAM (mRNA+) CTCs and Treg/CD4(+) cells showed significant correlation as prognostic factors of postoperative HCC recurrence: EpCAM (mRNA+) CTC ≥ 2.22 (P = 0.001) and Treg/CD4(+) ≥ 5.07 (P = 0.045), with EpCAM (mRNA+) CTC ≥ 2.22 (P = 0.003, HR = 6.668) being the most important indicator. Patients with high CTC/Treg levels showed a significantly higher risk of developing postoperative HCC recurrence than those with low CTC/Treg levels (66.7 % vs. 10.3 %, P < 0.001). The high CTC/low Treg group also presented higher 1-year recurrence rates compared with the low CTC/low Treg level group (50.0 % vs. 10.3 %, P = 0.004). Elevated EpCAM (mRNA+) CTC and Treg/CD4(+) levels were associated with early recurrence of HCC, indicative of poor clinical outcome. The combined detection of EpCAM (mRNA+) CTC and Treg/CD4(+) may therefore provide a novel prognostic predictor for HCC patients.