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Suppression of SAMSN1 Expression is Associated with the Malignant Phenotype of Hepatocellular Carcinoma

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Identification of molecular markers for sensitive detection of hepatocellular carcinoma (HCC) is required to achieve efficacious personalized therapy.

Methods

We focused here on SAM domain, SH3 domain, and nuclear localization signals 1 (SAMSN1) and investigated expression and methylation status of SAMSN1 in HCC cell lines and 144 pairs of surgical specimens.

Results

SAMSN1 was expressed at significantly lower levels in tumor tissue compared with the corresponding noncancerous tissues of patients with HCC. Analysis of HCC cell lines revealed that hypermethylation of the SAMSN1 promoter correlated with decreased expression of SAMSN1 mRNA. Furthermore, treating cells with a DNA-demethylating drug increased SAMSN1 transcription. The levels of SAMSN1 mRNA in noncancerous liver were not affected by background liver inflammation or fibrosis. Moreover, the levels of SAMSN1 mRNA in HCC tissues inversely correlated with tumor size and preoperative levels of proteins induced by vitamin K absence. The clinical significance of SAMSN1 was further indicated by the correlation between its decreased expression in patients with HCC and their shorter overall and recurrence-free survival as well as recurrence following initial resection. Moreover, multivariate analysis identified SAMSN1 as an independent prognostic factor of HCC progression. The expression pattern of SAMSN1 correlated significantly with that of SAMSN1 mRNA, making it possible to use PCR techniques to readily quantitate SAMSN1 expression in tumors.

Conclusions

Our findings indicate that inhibition of SAMSN1 transcription through DNA hypermethylation may influence the progression of HCC and thus represent a novel biomarker of the phenotype of HCC cells.

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Author notes

    Authors and Affiliations

    1. Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan

      Satoshi Sueoka MD, Mitsuro Kanda MD, PhD, Hiroyuki Sugimoto MD, PhD, Dai Shimizu MD, Hisaharu Oya MD, PhD, Hideki Takami MD, PhD, Kazuhiro Ezaka MD, Ryoji Hashimoto MD, Yuri Tanaka MD, Suguru Yamada MD, PhD, Tsutomu Fujii MD, PhD, Goro Nakayama MD, PhD, Masahiko Koike MD, PhD, Michitaka Fujiwara MD, PhD & Yasuhiro Kodera MD, PhD

    2. Department of Surgery, Aichi-Gakuin University School of Dentistry, Nagoya, Japan

      Shuji Nomoto MD, PhD

    3. Department of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan

      Yukiyasu Okamura MD, PhD

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    1. Satoshi Sueoka MD
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    Corresponding author

    Correspondence to Mitsuro Kanda MD, PhD.

    Additional information

    Satoshi Sueoka and Mitsuro Kanda have contributed equally to this work.

    Electronic supplementary material

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    10434_2015_4524_MOESM1_ESM.tif

    Supplementary material 1 RT-PCR analysis of the expression SAMSN1 expression in clinical specimens. (a) There were no significant differences in SAMSN1 mRNA levels among noncancerous tissues categorized by background uninvolved liver status. (b) SAMSN1 mRNA was expressed at lower levels in HCC tissues compared with those of the corresponding noncancerous tissues. (EPS 662 kb)

    10434_2015_4524_MOESM2_ESM.tif

    Supplementary material 2 (a) Correlation of SAMSN1 mRNA expression levels in HCC tissues with tumor size and (b) PIVKA II levels. (EPS 545 kb)

    10434_2015_4524_MOESM3_ESM.tif

    Supplementary material 3 SAMSN1 mRNA levels in HCC tissues categorized by the recurrence pattern at the initial (a) and second (b) recurrence. (EPS 17225 kb)

    Supplementary material 4 (DOC 41 kb)

    Supplementary material 5 (DOC 27 kb)

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    Sueoka, S., Kanda, M., Sugimoto, H. et al. Suppression of SAMSN1 Expression is Associated with the Malignant Phenotype of Hepatocellular Carcinoma. Ann Surg Oncol 22 (Suppl 3), 1453–1460 (2015). https://doi.org/10.1245/s10434-015-4524-1

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    • DOI: https://doi.org/10.1245/s10434-015-4524-1

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