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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

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.

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Acknowledgment

This research was supported by a National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (Grant number: NRF-2011-0013046 to Choi GH) (Grant number: NRF-2013R1A2A2A05005990, NRF-2011-0030086, NRF-2012M3A9B6055350 to Park YN). The authors thank to Dong-Su Jang, (Medical Illustrator, Medical Research Support Section, Yonsei University College of Medicine, Seoul, Korea) for help with the figures.

Conflict of interest

All authors have no conflict of interest.

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Correspondence to Young Nyun Park MD, PhD or Jin Sub Choi MD, PhD.

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Choi, G.H., Kim, G.I., Yoo, J.E. et al. Increased Expression of Circulating Cancer Stem Cell Markers During the Perioperative Period Predicts Early Recurrence After Curative Resection of Hepatocellular Carcinoma. Ann Surg Oncol 22 (Suppl 3), 1444–1452 (2015). https://doi.org/10.1245/s10434-015-4480-9

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  • DOI: https://doi.org/10.1245/s10434-015-4480-9

Keywords

  • Postoperative Recurrence
  • CD44 mRNA
  • Cancer Stem Cell Marker
  • Pugh Class
  • EpCAM mRNA