Gut Liver.  2022 May;16(3):443-455. 10.5009/gnl210162.

Circulating Cancer Stem Cells Expressing EpCAM/CD90 in Hepatocellular Carcinoma: A Pilot Study for Predicting Tumor Recurrence after Living Donor Liver Transplantation

Affiliations
  • 1Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
  • 2Department of Surgery, National Health Insurance Corporation Ilsan Hospital, Goyang, Korea
  • 3Department of Surgery, National Health Insurance Corporation Ilsan Hospital, Goyang, Korea
  • 4Yonsei Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Korea
  • 5The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea
  • 6Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Korea

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
Epithelial cell adhesion molecule+ (EpCAM+), cluster of differentiation 90+ (CD90+) and EpCAM+/CD90+ CTCs were sorted via fluorescence-activated cell sorting, and transcripts level of EpCAM, K19 and CD90 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.

Keyword

Circulating tumor cells; Hepatocellular carcinoma; Liver transplantation
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