Circulating Cancer Stem Cells Expressing EpCAM/CD90 in Hepatocellular Carcinoma: A Pilot Study for Predicting Tumor Recurrence after Living Donor Liver Transplantation
Hyeo Seong Hwang, Jeong Eun Yoo, Dai Hoon Han, Jin Sub Choi, Jae Geun Lee, Dong Jin Joo, Myoung Soo Kim, Soon Il Kim, Gi Hong Choi, Young Nyun Park
Abstract
Background/Aims: Circulating tumor cells (CTCs) with cancer stemness have been demonstrated to be a direct cause of tumor recurrence, and only few studies have reported the role of CTCs in liver transplantation (LT) for hepatocellular carcinoma (HCC). Methods: in the peripheral blood were analyzed via real-time polymerase chain reaction preoperatively and on postoperative days 1 and 7 in 25 patients who underwent living donor liver transplantation (LDLT) for HCC. EpCAM protein was assessed in HCC tissue using immunohistochemical staining. The median follow-up duration was 40 months. Results: HCC after LDLT recurred in four out of 25 patients. Detection of EpCAM+ or CD90+ CTCs correlated well with their messenger RNA levels (p<0.05). EpCAM+ CTCs were readily detected in HCC tissue expressing EpCAM protein. The detection of EpCAM+ CTCs or EpCAM+/CD90+ CTCs before surgery and on postoperative day 1 was significantly associated with HCC recurrence after LT (all p<0.05). Pretransplant serum PIVKA-II >100 mAU/mL and postoperative day 1 EpCAM+/CD90+ CTCs were independent risk factors for HCC recurrence (hazard ratio, 14.64; 95% confidence interval, 1.08 to 198.20; p=0.043 and hazard ratio, 26.88; 95% confidence interval, 1.86 to 387.51; p=0.016, respectively). Conclusions: EpCAM+/CD90+ CTCs can be used preoperatively and 1 day after LDLT as key biological markers in LT candidate selection and post-LDLT management.