title: B‑cell translocation gene 1 serves as a novel prognostic indicator of hepatocellular carcinoma.
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.
authors.affiliation: Department of Gastroenterological Surgery (Surgery Ⅱ), Nagoya University Graduate School of Medicine, Nagoya, Aichi 466‑8550, Japan.
authors.forename: Mitsuro
authors.initials: M
authors.lastname: Kanda
authors.affiliation: Department of Gastroenterological Surgery (Surgery Ⅱ), Nagoya University Graduate School of Medicine, Nagoya, Aichi 466‑8550, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sugimoto
authors.affiliation: Department of Gastroenterological Surgery (Surgery Ⅱ), Nagoya University Graduate School of Medicine, Nagoya, Aichi 466‑8550, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Nomoto
authors.affiliation: Department of Gastroenterological Surgery (Surgery Ⅱ), Nagoya University Graduate School of Medicine, Nagoya, Aichi 466‑8550, Japan.
authors.forename: Hisaharu
authors.initials: H
authors.lastname: Oya
authors.affiliation: Department of Gastroenterological Surgery (Surgery Ⅱ), Nagoya University Graduate School of Medicine, Nagoya, Aichi 466‑8550, Japan.
authors.forename: Soki
authors.initials: S
authors.lastname: Hibino
authors.affiliation: Department of Gastroenterological Surgery (Surgery Ⅱ), Nagoya University Graduate School of Medicine, Nagoya, Aichi 466‑8550, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Shimizu
authors.affiliation: Department of Gastroenterological Surgery (Surgery Ⅱ), Nagoya University Graduate School of Medicine, Nagoya, Aichi 466‑8550, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Takami
authors.affiliation: Department of Gastroenterological Surgery (Surgery Ⅱ), Nagoya University Graduate School of Medicine, Nagoya, Aichi 466‑8550, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Hashimoto
authors.affiliation: Division of Hepato‑Biliary‑Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka 411‑8777, Japan.
authors.forename: Yukiyasu
authors.initials: Y
authors.lastname: Okamura
authors.affiliation: Department of Gastroenterological Surgery (Surgery Ⅱ), Nagoya University Graduate School of Medicine, Nagoya, Aichi 466‑8550, Japan.
authors.forename: Suguru
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Department of Gastroenterological Surgery (Surgery Ⅱ), Nagoya University Graduate School of Medicine, Nagoya, Aichi 466‑8550, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Department of Gastroenterological Surgery (Surgery Ⅱ), Nagoya University Graduate School of Medicine, Nagoya, Aichi 466‑8550, Japan.
authors.forename: Goro
authors.initials: G
authors.lastname: Nakayama
authors.affiliation: Department of Gastroenterological Surgery (Surgery Ⅱ), Nagoya University Graduate School of Medicine, Nagoya, Aichi 466‑8550, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Koike
authors.affiliation: Department of Gastroenterological Surgery (Surgery Ⅱ), Nagoya University Graduate School of Medicine, Nagoya, Aichi 466‑8550, Japan.
authors.forename: Michitaka
authors.initials: M
authors.lastname: Fujiwara
authors.affiliation: Department of Gastroenterological Surgery (Surgery Ⅱ), Nagoya University Graduate School of Medicine, Nagoya, Aichi 466‑8550, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kodera
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis; D011401:Promoter Regions, Genetic
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; C074086:BTG1 protein, human