title: Preoperative serum methylation signature as prognostic tool after curative hepatectomy in patients with hepatocellular carcinoma.
abstract: OBJECTIVE
  This study aimed to investigate the relationship between prognosis after curative hepatectomy and serum methylation signature (SMS), defined by methylation levels of six specific genes (cyclin D2, Ras association (RalGDS/AF-6) domain family member 1, serine peptidase inhibitor Kunitz type 2, cystic fibrosis transmembrane conductance regulator, brain abundant membrane attached signal protein 1, and steroid-5-alpha-reductase alpha polypeptide 2).
  
  
  METHODS
  Serum samples were collected preoperatively from 125 patients with hepatocellular carcinoma associated with hepatitis C virus infection who underwent curative hepatectomy. We measured the methylation levels of the preceding six genes. We defined the methylation of three genes or more in the serum as SMS-positive in this study. We investigated the prognosis of SMS-positive patients.
  
  
  RESULTS
  SMS-positive patients exhibited significantly shorter disease-free survival (DFS) and overall survival (OS) than SMS-negative patients (p=0.0002 and p<0.0001, respectively). Multivariate analysis showed that SMS positivity was an independent risk factor for shorter DFS (hazard ratio (HR)=2.182; p<0.001) and OS (HR=4.198; p<0.001).
  
  
  CONCLUSIONS
  SMS is useful as a prognostic predictor in patients with hepatocellular carcinoma after curative hepatectomy.
authors: Department of Digestive Surgery and Surgical Oncology (Surgery II), Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan sin018@yamaguchi-u.ac.jp.
authors: Shinsuke
authors: S
authors: Kanekiyo
authors: Department of Digestive Surgery and Surgical Oncology (Surgery II), Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan Department of Kampo Medicine, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
authors: Norio
authors: N
authors: Iizuka
authors: Department of Digestive Surgery and Surgical Oncology (Surgery II), Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
authors: Ryoichi
authors: R
authors: Tsunedomi
authors: Department of Digestive Surgery and Surgical Oncology (Surgery II), Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
authors: Yukio
authors: Y
authors: Tokumitsu
authors: Department of Digestive Surgery and Surgical Oncology (Surgery II), Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
authors: Noriaki
authors: N
authors: Hashimoto
authors: Department of Digestive Surgery and Surgical Oncology (Surgery II), Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
authors: Yoshihiro
authors: Y
authors: Tokuhisa
authors: Department of Digestive Surgery and Surgical Oncology (Surgery II), Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
authors: Yoshinari
authors: Y
authors: Maeda
authors: Department of Digestive Surgery and Surgical Oncology (Surgery II), Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
authors: Michihisa
authors: M
authors: Iida
authors: Department of Digestive Surgery and Surgical Oncology (Surgery II), Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
authors: Kazuhiko
authors: K
authors: Sakamoto
authors: Department of Digestive Surgery and Surgical Oncology (Surgery II), Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
authors: Takao
authors: T
authors: Tamesa
authors: Department of Computer Science and Systems Engineering, Faculty of Engineering, Yamaguchi University, Ube, Yamaguchi, Japan.
authors: Yusuke
authors: Y
authors: Fujita
authors: Department of Digestive Surgery and Surgical Oncology (Surgery II), Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
authors: Shigefumi
authors: S
authors: Yoshino
authors: Department of Digestive Surgery and Surgical Oncology (Surgery II), Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
authors: Shoichi
authors: S
authors: Hazama
authors: Department of Computer Science and Systems Engineering, Faculty of Engineering, Yamaguchi University, Ube, Yamaguchi, Japan.
authors: Yoshihiko
authors: Y
authors: Hamamoto
authors: Department of Digestive Surgery and Surgical Oncology (Surgery II), Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
authors: Masaaki
authors: M
authors: Oka
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000473:pathology / Q000601:surgery*; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000473:pathology / Q000601:surgery*; D008745:Methylation; D011379:Prognosis
keywords: HCC; cell-free DNA; epigenetic; methylation; quantitative MSP