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High expression of Snail mRNA in blood from hepatocellular carcinoma patients with extra-hepatic metastasis

  • Ae Lyoung Min
  • Jong Young Choi
  • Hyun Young Woo
  • Jin Dong Kim
  • Jung Hyun Kwon
  • Si Hyun Bae
  • Seung Kew Yoon
  • Seung Hun Shin
  • Yeun Jun Chung
  • Chan Kwon Jung
Research Paper

Abstract

The presence of circulating tumor cells (CTCs) in patients with hepatocellular carcinoma (HCC) suggests metastasis to extra-hepatic organs. Snail is a key regulator of epithelial mesenchymal transition, which is closely associated with tumor metastasis. The aim of this study was to investigate the presence of CTCs and evaluate the significance of Snail mRNA levels in peripheral blood of HCC patients with and without extra-hepatic metastasis. Sixty-six consecutive patients with HCC (30 without metastasis, 36 with metastasis) were prospectively enrolled, as were 30 with liver cirrhosis and 23 healthy subjects. CTCs were isolated by FACS using Ber-EP4 and anti-CD45 antibodies, and CTC identity confirmed by immunofluorescent cytokeratin staining. Snail mRNA levels were measured by quantitative real-time PCR of blood samples. CTCs, positive for pan-cytokeratin and Snail, were isolated from five HCC patients with metastasis. The mean amount of Snail mRNA in HCC with metastasis was 18.8-fold, 26.6-fold greater than HCC without metastasis, liver cirrhosis, respectively. When compared with healthy controls, the mean level of Snail mRNA in HCC without metastasis was 10.1-fold greater (P < 0.001). In six patients showing complete remission of HCC, Snail mRNA decreased to levels similar to those of healthy controls. This study suggests the possibility that circulating Snail mRNA levels may have been associated with extra-hepatic metastasis in HCC patients.

Keywords

Hepatocellular Carcinoma Circulating tumor cell Snail Metastasis 

Abbreviations

HCC

Hepatocellular carcinoma

CTC

Circulating tumor cell

EMT

Epithelial mesenchymal transition

AFP

Alpha-fetoprotein

FACS

Fluorescence activated cell sorter

PBMC

Peripheral blood mononuclear cell

RT-PCR

Reverse-transcription polymerase chain reaction

qRT-PCR

Quantitative real-time PCR

Notes

Acknowledgments

This study was supported in part by grant of the Leading Foreign Research Institute Recruitment Program and from FG06-12-01 of the 21C Frontier Functional Human Genome Project from the Ministry of Science & Technology in Korea.

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Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Ae Lyoung Min
    • 1
  • Jong Young Choi
    • 1
    • 4
  • Hyun Young Woo
    • 1
  • Jin Dong Kim
    • 1
  • Jung Hyun Kwon
    • 1
  • Si Hyun Bae
    • 1
  • Seung Kew Yoon
    • 1
  • Seung Hun Shin
    • 2
  • Yeun Jun Chung
    • 2
  • Chan Kwon Jung
    • 3
  1. 1.Department of Internal Medicine, College of MedicineThe Catholic University of KoreaSeoulKorea
  2. 2.Department of Microbiology, College of MedicineThe Catholic University of KoreaSeoulKorea
  3. 3.Department of Hospital Pathology, College of MedicineThe Catholic University of KoreaSeoulKorea
  4. 4.Department of Internal Medicine, College of MedicineThe Catholic University of KoreaSeoulKorea

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