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

Yan Zhou,Yiwen Zhou,Beili Wang,Wei Guo,Jia Fan,Jian Zhou,Xinrong Yang,Chunyan Zhang,Jiong Wu

doi:10.1186/s12885-016-2526-4

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.

Highlights

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
EpCAM messenger RNA (mRNA)+ CTCs and Treg/CD4+ cells definition According to previous studies, the prognostic cut-off value for HCC recurrence of EpCAMmRNA+ CTCs (2−ΔΔCT) was 2.0 [9]
The optimal prognostic cut-off values calculated by X-tile 3.6.1 software for EpCAM mRNA+ CTCs (2−ΔΔCT) and Treg/CD4+ (%) were 2.22 and 5.07, respectively

Summary

Introduction

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. Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide, and is ranked second in global cancer-related mortality. The high incidence and poor prognosis of HCC are current focuses of clinical research [1]. The main treatments for HCC include surgical resection and liver transplantation. The tumor recurrence rate exceeds 70 % after 5 years following resection, and recurrence is considered the main contributor to mortality [2]. It is critical to find robust prognostic biomarkers with which to monitor postoperative recurrence for HCC patients [4]

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