title: Suppression of SAMSN1 Expression is Associated with the Malignant Phenotype of Hepatocellular Carcinoma.
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.
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Satoshi
authors: S
authors: Sueoka
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan. m-kanda@med.nagoya-u.ac.jp.
authors: Mitsuro
authors: M
authors: Kanda
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Hiroyuki
authors: H
authors: Sugimoto
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Dai
authors: D
authors: Shimizu
authors: Department of Surgery, Aichi-Gakuin University School of Dentistry, Nagoya, Japan.
authors: Shuji
authors: S
authors: Nomoto
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Hisaharu
authors: H
authors: Oya
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Hideki
authors: H
authors: Takami
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Kazuhiro
authors: K
authors: Ezaka
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Ryoji
authors: R
authors: Hashimoto
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Yuri
authors: Y
authors: Tanaka
authors: Department of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan.
authors: Yukiyasu
authors: Y
authors: Okamura
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Suguru
authors: S
authors: Yamada
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Tsutomu
authors: T
authors: Fujii
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Goro
authors: G
authors: Nakayama
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Masahiko
authors: M
authors: Koike
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Michitaka
authors: M
authors: Fujiwara
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Yasuhiro
authors: Y
authors: Kodera
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D016022:Case-Control Studies; D019175:DNA Methylation; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D008297:Male; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D009367:Neoplasm Staging; D010641:Phenotype; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C435526:SAMSN1 protein, human