Kanekiyo Shinsuke, Iizuka Norio, Tsunedomi Ryoichi, Tokumitsu Yukio, Hashimoto Noriaki, Tokuhisa Yoshihiro, Maeda Yoshinari, Iida Michihisa, Sakamoto Kazuhiko, Tamesa Takao, Fujita Yusuke, Yoshino Shigefumi, Hazama Shoichi, Hamamoto Yoshihiko, Oka Masaaki
Department of Digestive Surgery and Surgical Oncology (Surgery II), Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
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.
Anticancer Res. 2015 Feb;35(2):997-1007.
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).
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.
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).
SMS is useful as a prognostic predictor in patients with hepatocellular carcinoma after curative hepatectomy.
