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.

NRAGE promotes the malignant phenotype of hepatocellular carcinoma

“…The HCC cell lines (Hep3B, HepG2, HLE, HLF, HuH1, HuH2, HuH7, PLC/PRF/5 and SK-Hep1) were obtained from the American Type Culture Collection (Manassas, VA, USA). All cell lines were cultured in Dulbecco's modified Eagle's Medium (Sigma-Aldrich, St. Louis, MO, USA), supplemented with 10% fetal bovine serum at 37˚C in an atmosphere containing 5% CO 2 (6). The primary HCC tissues and the corresponding non-cancerous tissues were collected from 151 patients with HCC who had undergone liver resection at the Nagoya University Hospital (Nagoya, Japan) between January 1998 and July 2012.…”

“…An important strategy to improve patient outcome involves the identification of disease risk factors and the maintenance of vigilant surveillance of high-risk individuals to allow for recognition of the disease at a stage that is responsive to treatment with curative intent. Therefore, it is fundamental that high-risk groups are identified, followed by successful implementation of a surveillance program and recall protocol following any abnormal findings (5)(6)(7)(8). Progress has been made in identifying molecular markers for the initiation and progression of HCC that will likely increase the rate of early and potentially life-saving diagnoses (9)(10)(11)(12).…”

Reduced Expression of Adherens Junctions Associated Protein 1 Predicts Recurrence of Hepatocellular Carcinoma After Curative Hepatectomy

“…The corresponding noncancerous liver tissue samples lacking regenerative or dysplastic nodules were collected [2 cm from the edge of the tumor from the same patient. 19,20 Postoperative follow-up included physical examinations, measurement of serum tumor markers every 3 months, and enhanced computed tomography every 6 months. Treatment after recurrence included surgery, radiofrequency ablation, transcatheter arterial chemoembolization, and chemotherapy, according to tumor status and liver function.…”

Translational implication of Kallmann syndrome-1 gene expression in hepatocellular carcinoma

“…KAL1 protein localization was determined by IHC using 64 representative formalin-fixed and paraffin-embedded sections of wellpreserved HCC tissue using a rabbit polyclonal antibody against KAL1 (ABN486, Millipore, Darmstadt, germany) diluted 1:150 in antibody diluent (Dako, glostrup, Denmark) as previously described (7,31). samples were then washed with phosphate-buffered saline, followed by 10 min incubation with a biotinylated secondary antibody (Histofine sAB-PO(R), Nichirei, Tokyo, japan).…”

“…Aberrant DNA methylation is one of the most common epigenetic alterations in malignancies and is specific to individual organs and diseases (6)(7)(8). Furthermore, several studies have shown that aberrant DNA methylation contributes to the initiation and progression of malignant tumors through inactivation of tumor suppressors (9,10).…”