B‑cell translocation gene 1 serves as a novel prognostic indicator of hepatocellular carcinoma

Kanda,Mitsuro; Sugimoto,Hiroyuki; Nomoto,Shuji; Oya,Hisaharu; Hibino,Soki; Shimizu,Dai; Takami,Hideki; Hashimoto,Ryoji; Okamura,Yukiyasu; Yamada,Suguru; Fujii,Tsutomu; Nakayama,Goro; Koike,Masahiko; Fujiwara,Michitaka; Kodera,Yasuhiro

doi:10.3892/ijo.2014.2762

B‑cell translocation gene 1 serves as a novel prognostic indicator of hepatocellular carcinoma

Authors:
- Mitsuro Kanda
- Hiroyuki Sugimoto
- Shuji Nomoto
- Hisaharu Oya
- Soki Hibino
- Dai Shimizu
- Hideki Takami
- Ryoji Hashimoto
- Yukiyasu Okamura
- Suguru Yamada
- Tsutomu Fujii
- Goro Nakayama
- Masahiko Koike
- Michitaka Fujiwara
- Yasuhiro Kodera
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Affiliations: Department of Gastroenterological Surgery (Surgery Ⅱ), Nagoya University Graduate School of Medicine, Nagoya, Aichi 466‑8550, Japan, Division of Hepato‑Biliary‑Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka 411‑8777, Japan
Published online on: November 18, 2014 https://doi.org/10.3892/ijo.2014.2762
Pages: 641-648

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Abstract

Although the B‑cell translocation gene 1 (BTG1) plays an important role in apoptosis and negatively regulates cell proliferation, BTG1 expression in hepatocellular carcinoma (HCC) has not been evaluated. In this study expression analysis of BTG1 was conducted to clarify the role of BTG1 in the initiation of HCC carcinogenesis and progression. BTG1 mRNA expression levels were determined for HCC cell lines and 151 surgical specimen pairs using quantitative real‑time reverse transcription polymerase chain reaction (RT‑qPCR) assay. The mutational and methylation status of HCC cell lines were analyzed via high resolution melting (HRM) analysis and direct sequencing analysis to elucidate the regulatory mechanisms of BTG1 expression. The expression and distribution of the BTG1 protein in liver tissues were evaluated using immunohistochemistry (IHC). Decreased expression of BTG1 mRNA was confirmed in the majority of HCC cell lines (89%) and clinical HCC tissues (85%) compared with non‑cancerous liver tissues. Mutations or promoter hypermethylation were not identified in HCC cell lines. BTG1 mRNA expression levels were not influenced by background liver status. The pattern of BTG1 protein expression was consistent with that of BTG1 mRNA. Downregulation of BTG1 mRNA in HCC was significantly associated with shorter disease‑specific and recurrence‑free survival rates. Multivariate analysis of disease‑specific survival rates identified BTG1 mRNA downregulation as an independent prognostic factor for HCC (hazard ratio 2.12, 95% confidence interval 1.12‑4.04, P=0.022). Our results indicate that altered BTG1 expression might affect hepatocarcinogenesis and may represent a novel biomarker for HCC carcinogenesis and progression.

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