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Increased Expression of Circulating Cancer Stem Cell Markers During the Perioperative Period Predicts Early Recurrence After Curative Resection of Hepatocellular Carcinoma

 Gi Hong Choi  ;  Gwang Il Kim  ;  Jeong Eun Yoo  ;  Deuk Chae Na  ;  Dai Hoon Han  ;  Yun Ho Roh  ;  Young Nyun Park  ;  Jin Sub Choi 
 ANNALS OF SURGICAL ONCOLOGY, Vol.22(Suppl 3) : S1444-S1452, 2015 
Journal Title
Issue Date
Adult ; Aged ; Biomarkers, Tumor/blood* ; Carcinoma, Hepatocellular/blood* ; Carcinoma, Hepatocellular/pathology ; Carcinoma, Hepatocellular/surgery ; Female ; Follow-Up Studies ; Hepatectomy ; Humans ; Immunoenzyme Techniques ; Liver Neoplasms/blood* ; Liver Neoplasms/pathology ; Liver Neoplasms/surgery ; Liver Transplantation ; Male ; Middle Aged ; Neoplasm Recurrence, Local/blood* ; Neoplasm Recurrence, Local/pathology ; Neoplasm Recurrence, Local/surgery ; Neoplasm Staging ; Neoplastic Cells, Circulating/pathology* ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology* ; Perioperative Period ; Prognosis ; Prospective Studies ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Survival Rate
Postoperative Recurrence ; CD44 mRNA ; Cancer Stem Cell Marker ; Pugh Class ; EpCAM mRNA
BACKGROUND: This study was designed to investigate the correlation between postoperative recurrence of hepatocellular carcinoma (HCC) and perioperative expression and dynamic changes in cancer stem cell (CSC) markers in tumors and peripheral blood.

METHODS: In HCC patients who underwent curative resection (n = 64) or liver transplantation (LT) (n = 17), mRNA levels for K19, EpCAM, and CD44 in peripheral blood and HCC tissues before and after operation were examined using real-time RT-PCR. Postoperative recurrence was analyzed in patients who underwent resection. Study participants were divided into high and low ratio groups, according to the ratio of postoperative to preoperative mRNA levels for each marker.

RESULTS: K19 and CD44 mRNA levels in HCC tissues were higher in patients with recurrence than those without recurrence (p < 0.05 for all). Preoperative peripheral levels of K19 and EpCAM mRNA were higher in LT patients than in resection patients, and they were also significantly higher in cirrhotic patients of Child-Pugh Class B or C than those of Child-Pugh Class A (p < 0.05 for all). A high ratio of K19 mRNA was associated with lower relapse-free rate. Additionally, a high ratio for both K19 and CD44 mRNA was an independent poor prognostic factor for relapse-free survival (hazard ratio = 3.382, p = 0.016).

CONCLUSIONS: Preoperative peripheral levels of K19 and EpCAM mRNA were influenced by background liver status and HCC. Additionally, the ratio of postoperative to preoperative mRNA levels for CSC markers, especially K19 and CD44, was shown to be important to predict HCC recurrence.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biomedical Systems Informatics (의생명시스템정보학교실) > 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
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Gwang Il(김광일)
Na, Deuk Chae(나득채)
Roh, Yun Ho(노윤호)
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
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
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