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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 
 GUT AND LIVER, Vol.16(3) : 443-455, 2022-05 
Journal Title
Issue Date
Carcinoma, Hepatocellular* / genetics ; Carcinoma, Hepatocellular* / surgery ; Epithelial Cell Adhesion Molecule / analysis ; Epithelial Cell Adhesion Molecule / metabolism ; Humans ; Liver Neoplasms* / pathology ; Liver Neoplasms* / surgery ; Liver Transplantation* ; Living Donors ; Neoplasm Recurrence, Local / metabolism ; Neoplastic Stem Cells / metabolism ; Pilot Projects ; Thy-1 Antigens / metabolism*
Circulating tumor cells ; Hepatocellular carcinoma ; Liver transplantation
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.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Myoung Soo(김명수) ORCID logo https://orcid.org/0000-0002-8975-8381
Kim, Soon Il(김순일) ORCID logo https://orcid.org/0000-0002-0783-7538
Park, Young Nyun(박영년) ORCID logo https://orcid.org/0000-0003-0357-7967
Yoo, Jeong Eun(유정은) ORCID logo https://orcid.org/0000-0001-9990-279X
Lee, Jae Geun(이재근) ORCID logo https://orcid.org/0000-0002-6722-0257
Joo, Dong Jin(주동진) ORCID logo https://orcid.org/0000-0001-8405-1531
Choi, Gi Hong(최기홍) ORCID logo https://orcid.org/0000-0002-1593-3773
Choi, Jin Sub(최진섭)
Han, Dai Hoon(한대훈) ORCID logo https://orcid.org/0000-0003-2787-7876
Hwang, Hyeoseong(황혜성)
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