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Circulating stem cell–like epithelial cell adhesion molecule–positive tumor cells indicate poor prognosis of hepatocellular carcinoma after curative resection
Author(s) -
Sun YunFan,
Xu Yang,
Yang XinRong,
Guo Wei,
Zhang Xin,
Qiu ShuangJian,
Shi RuoYu,
Hu Bo,
Zhou Jian,
Fan Jia
Publication year - 2013
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.26151
Subject(s) - epithelial cell adhesion molecule , circulating tumor cell , hepatocellular carcinoma , medicine , stem cell , cancer stem cell , mesenchymal stem cell , oncology , carcinoma , cancer research , pathology , gastroenterology , cancer , metastasis , biology , genetics
Epithelial cell adhesion molecule–positive (EpCAM + ) hepatocellular carcinoma (HCC) cells may constitute a tumor‐initiating subpopulation in tumorigenic cell lines and HCC specimens. In the present study, EpCAM + circulating tumor cells (CTCs) were identified prospectively in HCC patients undergoing curative resection, and the prognostic significance and their stem cell–like characteristics were investigated further. Blood samples from 123 HCC patients were tested prior to resection and 1 month thereafter. CTCs were present in 66.67% of patients, and the cell count measured in 7.5 mL of blood (CTC 7.5 ) ranged between 1 and 34. Fifty‐one patients had CTC 7.5 of ≥2 preoperatively, and these patients developed tumor recurrence earlier than those with CTC 7.5 of <2 CTCs ( P < 0.001). A preoperative CTC 7.5 of ≥2 was an independent prognostic factor for tumor recurrence ( P < 0.001). Its prognostic significance also applied to patients with alpha‐fetoprotein (AFP) levels of ≤400 ng/mL or subgroups with low recurrence risk (all P < 0.05). A significant decrease of CTC‐positive rates (66.67% to 28.15%, P < 0.05) and CTC 7.5 values (2.60 ± 0.43 to 1.00 ± 0.36, P < 0.05) was observed 1 month after resection. Patients with consistent CTC 7.5 <2 had lower recurrence rates than those with values consistently ≥2 (15.5% versus 87.50%, P < 0.001). EpCAM + CTCs displayed cancer stem cell biomarkers (CD133 and ABCG2), epithelial‐mesenchymal transition, Wnt pathway activation, high tumorigenic potential, and low apoptotic propensity. Conclusion : Stem cell–like phenotypes are observed in EpCAM + CTCs, and a preoperative CTC 7.5 of ≥2 is a novel predictor for tumor recurrence in HCC patients after surgery, especially in patient subgroups with AFP levels of ≤400 ng/mL or low tumor recurrence risk. EpCAM + CTCs may serve as a real‐time parameter for monitoring treatment response and a therapeutic target in HCC recurrence. (H EPATOLOGY 2013)