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

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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.

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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

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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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Authors and Affiliations

  1. Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea

    Ae Lyoung Min, Jong Young Choi, Hyun Young Woo, Jin Dong Kim, Jung Hyun Kwon, Si Hyun Bae & Seung Kew Yoon

  2. Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Korea

    Seung Hun Shin & Yeun Jun Chung

  3. Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea

    Chan Kwon Jung

  4. Department of Internal Medicine, College of Medicine, The Catholic University of Korea, #505 Banpodong, Seocho-ku, Seoul, 137-040, Korea

    Jong Young Choi

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  1. Ae Lyoung Min
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Correspondence to Jong Young Choi.

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Min, A.L., Choi, J.Y., Woo, H.Y. et al. High expression of Snail mRNA in blood from hepatocellular carcinoma patients with extra-hepatic metastasis. Clin Exp Metastasis 26, 759–767 (2009). https://doi.org/10.1007/s10585-009-9275-6

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  • DOI: https://doi.org/10.1007/s10585-009-9275-6

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