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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 3/2015

01-12-2015 | Translational Research and Biomarkers

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

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

Published in: Annals of Surgical Oncology | Special Issue 3/2015

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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.
Appendix
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Metadata
Title
Suppression of SAMSN1 Expression is Associated with the Malignant Phenotype of Hepatocellular Carcinoma
Authors
Satoshi Sueoka, MD
Mitsuro Kanda, MD, PhD
Hiroyuki Sugimoto, MD, PhD
Dai Shimizu, MD
Shuji Nomoto, MD, PhD
Hisaharu Oya, MD, PhD
Hideki Takami, MD, PhD
Kazuhiro Ezaka, MD
Ryoji Hashimoto, MD
Yuri Tanaka, MD
Yukiyasu Okamura, MD, PhD
Suguru Yamada, MD, PhD
Tsutomu Fujii, MD, PhD
Goro Nakayama, MD, PhD
Masahiko Koike, MD, PhD
Michitaka Fujiwara, MD, PhD
Yasuhiro Kodera, MD, PhD
Publication date
01-12-2015
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue Special Issue 3/2015
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-015-4524-1

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