Circulating Cancer Stem Cells in Hepatocellular Carcinoma: A Pilot Study of Prediction for Tumor Recurrence after Living Donor Liver Transplantation

Abstract

Introduction: The optimal indication of LT in HCC patients has evolved from Milan criteria to morphologic criteria with biologic markers. The role of circulating cancer stem cells has not been reported in patients who underwent LT for HCC. Method: From April 2014 to March 2017, 25 patients who underwent LDLT for HCC were prospectively enrolled. EpCAM, CD90 and EpCAM/CD90 were sorted by FACS and mRNA expression of EPCAM, KRT19, THY1 were analyzed by RT-PCR in peripheral blood at preoperative, postoperative day 1 and 7, respectively. The median follow-up duration was 40 months. Results: The mean age was 55.9 years, and HBV was the most common underlying liver disease (88%). 10 patients were above Milan criteria at diagnosis. HCC recurred in 4 patients. The detected numbers of EpCAM (+) cells and CD90 (+) cells were well correlated with mRNA expression levels in the peripheral blood (P< 0.05). EpCAM protein in HCC tissue was highly expressed in patients with recurrence (66% vs. 20%). (p=0.172). HCCs with EpCAM (+) protein expression showed more detection of EpCAM (+) circulating cells than EpCAM (-). The detection of EpCAM (+) or EpCAM(+)/CD90(+) cells before surgery and at postoperative day 1 were significantly associated with HCC recurrence after LT (p< 0.05 for all). Conclusion: Detection of EpCAM (+) or EpCAM(+)/CD90(+) cells in the peripheral blood before surgery and at postoperative day 1 was the only variable significantly associated with HCC recurrence after LDLT but should be validated in a large-scale prospective study.