Gi Hong Choi1,2, Gwang Il Kim3, Jeong Eun Yoo3, Deuk Chae Na3, Dai Hoon Han1,2, Yun Ho Roh4, Young Nyun Park5,6,7, Jin Sub Choi8,9. 1. Department of Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemoon-gu, Seoul, 120-752, Korea. 2. Yonsei Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Korea. 3. Department of Pathology and Integrated Genomic Research Center for Metabolic Regulation, Yonsei University College of Medicine, Seoul, Korea. 4. Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Korea. 5. Department of Pathology and Integrated Genomic Research Center for Metabolic Regulation, Yonsei University College of Medicine, Seoul, Korea. young0608@yuhs.ac. 6. BK21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. young0608@yuhs.ac. 7. Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea. young0608@yuhs.ac. 8. Department of Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemoon-gu, Seoul, 120-752, Korea. Choi5491@yuhs.ac. 9. Yonsei Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Korea. Choi5491@yuhs.ac.
Abstract
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.
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.
Authors: Yangyang Hu; Lin Lu; Yang Xia; Xin Chen; Alfred E Chang; Robert E Hollingsworth; Elaine Hurt; John Owen; Jeffrey S Moyer; Mark E P Prince; Fu Dai; Yangyi Bao; Yi Wang; Joel Whitfield; Jian-Chuan Xia; Shiang Huang; Max S Wicha; Qiao Li Journal: Cancer Res Date: 2016-06-20 Impact factor: 12.701