Prognostic Significance of BCL9 Expression in Hepatocellular Carcinoma
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background: BCL9 enhances β-catenin-mediated transcriptional activity regardless of the mutational status of the Wnt signaling components and increases the cell proliferation, migration, invasion, and metastatic potential of tumor cells. The goal of this study was to elucidate the prognostic significance of BCL9 protein expression in hepatocellular carcinoma (HCC) patients. Methods: We evaluated BCL9 protein expression by immunohistochemistry in tumor tissue from 288 primary HCC patients who underwent curative hepatectomy. The impact of BCL9 expression on the survival of the patients was analyzed. The median follow-up period was 97.1 months. Results: Nuclear BCL9 protein expression was observed in 74 (25.7%) of the 288 HCCs. BCL9 expression was significantly associated with younger age (p=0.038), higher Edmondson grade (p=0.001), microvascular invasion (p=0.013), and intrahepatic metastasis (p=0.017). Based on univariate analyses, BCL9 expression showed an unfavorable influence on both disease-free survival (DFS, p=0.012) and disease-specific survival (DSS, p=0.032). Multivariate analyses revealed that higher Barcelona Clinic Liver Cancer stage was an independent predictor of both shorter DFS (p<0.001) and shorter DSS (p<0.001). BCL9 expression tended to be an independent predictor of shorter DFS (p=0.078). Conclusions: BCL9 protein expression might be a marker of shorter DFS in HCC patients after curative hepatectomy.
Abstract
Background: BCL9 enhances β-catenin-mediated transcriptional activity regardless of the mutational status of the Wnt signaling components and increases the cell proliferation, migration, invasion, and metastatic potential of tumor cells. The goal of this study was to elucidate the prognostic significance of BCL9 protein expression in hepatocellular carcinoma (HCC) patients. Methods: We evaluated BCL9 protein expression by immunohistochemistry in tumor tissue from 288 primary HCC patients who underwent curative hepatectomy. The impact of BCL9 expression on the survival of the patients was analyzed. The median follow-up period was 97.1 months. Results: Nuclear BCL9 protein expression was observed in 74 (25.7%) of the 288 HCCs. BCL9 expression was significantly associated with younger age (p=0.038), higher Edmondson grade (p=0.001), microvascular invasion (p=0.013), and intrahepatic metastasis (p=0.017). Based on univariate analyses, BCL9 expression showed an unfavorable influence on both disease-free survival (DFS, p=0.012) and disease-specific survival (DSS, p=0.032). Multivariate analyses revealed that higher Barcelona Clinic Liver Cancer stage was an independent predictor of both shorter DFS (p<0.001) and shorter DSS (p<0.001). BCL9 expression tended to be an independent predictor of shorter DFS (p=0.078). Conclusions: BCL9 protein expression might be a marker of shorter DFS in HCC patients after curative hepatectomy.
참고문헌 (19)
- Poon RT, "Prevention of recurrence after resection of hepatocellular carcinoma: a daunting challenge", Hepatology, 54, pp.757~759 (2011)
- Llovet JM, "Resection and liver transplantation for hepatocellular carcinoma", Semin Liver Dis, 25, pp.181~200 (2005)
- Qin LX, "Recent progress in predictive biomarkers for metastatic recurrence of human hepatocellular carcinoma: a review of the literature", J Cancer Res Clin Oncol, 130, pp.497~513 (2004)
- Willis TG, "Molecular cloning of translocation t(1;14)(q21;q32) defines a novel gene (BCL9) at chromosome 1q21", Blood, 91, pp.1873~1881 (1998)
- Kramps T, "Wnt", wingless signaling requires BCL9, Cell, pp.2002, 109[DOI]
- Polakis P, "Wnt signaling and cancer", Genes Dev, 14, pp.1837~1851 (2000)
- Morin PJ, "Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC", Science, 275, pp.1787~1790 (1997)
- Mani M, "BCL9 promotes tumor progression by conferring enhanced proliferative, metastatic, and angiogenic properties to cancer cells", Cancer Res, 69, pp.7577~7586 (2009)
- Brembeck FH, "BCL9-2 promotes early stages of intestinal tumor progression", Gastroenterology, 141, pp.1359~1370 (2011)
- Kim TM, "Clinical implication of recurrent copy number alterations in hepatocellular carcinoma and putative oncogenes in recurrent gains on 1q", Int J Cancer, 123, pp.2808~2815 (2008)
- Moinzadeh P, "Chromosome alterations in human hepatocellular carcinomas correlate with aetiology and histological grade: results of an explorative CGH metaanalysis", Br J Cancer, 92, pp.935~941 (2005)
- Wong N, "Assessment of genetic changes in hepatocellular carcinoma by comparative genomic hybridization analysis: relationship to disease stage, tumor size, and cirrhosis", Am J Pathol, 154, pp.37~43 (1999)
- Edmondson HA, "Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies", Cancer, 7, pp.462~503 (1954)
- Liver Cancer Study Group of Japan, "General rules for the clinical and pathological study of primary liver cancer", pp.38~ (2003), Kanehara
- Edge SB, "Trotti A 3rd. AJCC cancer staging manual" (2010), Springer
- Llovet JM, "Prognosis of hepatocellular carcinoma: the BCLC staging classification", Semin Liver Dis, 19, pp.329~338 (1999)
- Hoshida Y, "Gene expression in fixed tissues and outcome in hepatocellular carcinoma", N Engl J Med, 359, pp.1995~2004 (2008)
- International Working Party, "Terminology of nodular hepatocellular lesions", Hepatology, 22, pp.983~993 (1995)
- Kim SH, "Smad3 and its phosphoisoforms are prognostic predictors of hepatocellular carcinoma after curative hepatectomy", Hepatobiliary Pancreat Dis Int, 11, pp.51~59 (2012)