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

Abstract

BackgroundThis 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.MethodsA 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 EpCAMmRNA+ CTCs and CD4+CD25+Foxp3+ Treg cells. The prognostic value of EpCAMmRNA+ 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.ResultsThe number of EpCAMmRNA+ CTCs and Treg/CD4+ cells showed significant correlation as prognostic factors of postoperative HCC recurrence: EpCAMmRNA+ CTC ≥ 2.22 (P = 0.001) and Treg/CD4+ ≥ 5.07 (P = 0.045), with EpCAMmRNA+ 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).ConclusionsElevated EpCAMmRNA+ CTC and Treg/CD4+ levels were associated with early recurrence of HCC, indicative of poor clinical outcome. The combined detection of EpCAMmRNA+ CTC and Treg/CD4+ may therefore provide a novel prognostic predictor for HCC patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2526-4) contains supplementary material, which is available to authorized users.

RNA-seq reveals distinctive RNA profiles of small extracellular vesicles from different human liver cancer cell lines

“…The western blots revealed the presence of EpCAM in all EVs and, to a greater extent, in Hep-3B and HepG2-EVs. EpCAM is a “stem-associated” marker and has been linked to poor outcome in HCC [ 34 ], suggesting that it could be used as a prognostic predictor to test for HCC recurrence in patients [ 35 , 36 ]. We found TGM2 in the EVs released by all cell lines, in agreement with other studies demonstrating that TGM2 is a hepatoma-related protein and may be a candidate for use as an HCC marker [ 26 ].…”

How does the tumor microenvironment play a role in hepatobiliary tumors?

“…The presence of EpCAM+ cells in liver tissue has been associated with a higher AFP level and worse prognosis. Moreover, the presence of systemic circulating EpCAM+ hepatic stem cells were also associated with worse prognosis and early recurrence after curative surgery (61,62). This is thought to be secondary to the stem cells' overexpression of the Wnt β-catenin pathway and was demonstrated to induce chemoresistance to doxorubicin and sorafenib (63).…”

Overexpression of epithelial cell adhesion molecule as a predictor of poor outcome in patients with hepatocellular carcinoma

“…Circulating tumor cells spread from the primary sites into the peripheral blood supply and arrive at the metastasis site; this process involves many genes (11,12). Recurrent, high-grade and distant metastases indicate invasive circulating tumor cells, which are responsible for poor prognosis in HCC patients (13). A transmembrane glycoprotein-epithelial cell adhesion molecule (EpCAM; CD326) serves an important role in the distant metastasis of HCC (14).…”