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Erschienen in: Tumor Biology 2/2013

01.04.2013 | Research Article

Prognostic significance of BMP7 as an oncogene in hepatocellular carcinoma

verfasst von: Wei Li, Hong-Xin Cai, Xu-Ming Ge, Kai Li, Wei-Dong Xu, Wei-Hong Shi

Erschienen in: Tumor Biology | Ausgabe 2/2013

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Abstract

This study aims to evaluate the association between BMP7 tissue expression and patient prognosis in hepatocellular carcinoma (HCC). The expression of BMP7 mRNA in HCC was characterized using real-time PCR and 30 pairs of fresh frozen HCC tissues and corresponding noncancerous tissues. BMP7 protein expression in HCC was confirmed using immunohistochemistry on a tissue microarray chip. Finally, BMP7 expression was correlated with conventional clinicopathological features of HCC and patient outcome. The expression of BMP7 mRNA and protein in HCC cells was much higher than in normal hepatic cells. Our results showed that the high expression of BMP7 in HCC was related to tumor size (p < 0.001), histological differentiation (p = 0.041), serum AFP (p = 0.007), and tumor stage (p < 0.001). Kaplan–Meier survival analysis showed that a high-expression level of BMP7 resulted in a significantly poor prognosis of HCC patients. Multivariate analysis revealed that BMP7 expression level was an independent prognostic parameter for the overall survival rate of HCC patients. These findings provide evidence that a high-expression level of BMP7 serves as a biomarker for poor prognosis for HCC. Thus, we speculate that BMP7 may be a potential target of antiangiogenic therapy for HCC.
Literatur
1.
Zurück zum Zitat Shariff MI, Cox IJ, Gomaa AI, Khan SA, Gedroyc W, TaylorRobinson SD. Hepatocellular carcinoma:current trends in worldwide epidemiology, risk factors, diagnosis and therapeutics. Expert Rev Gastroenterol Hepatol. 2009;3:353–67. doi:10.1586/egh.09.35.PubMedCrossRef Shariff MI, Cox IJ, Gomaa AI, Khan SA, Gedroyc W, TaylorRobinson SD. Hepatocellular carcinoma:current trends in worldwide epidemiology, risk factors, diagnosis and therapeutics. Expert Rev Gastroenterol Hepatol. 2009;3:353–67. doi:10.​1586/​egh.​09.​35.PubMedCrossRef
2.
Zurück zum Zitat Lau WY, Lai EC. Hepatocellular carcinoma: current management and recent advances. Hepatobiliary Pancreat Dis Int. 2008;7:237–57.PubMed Lau WY, Lai EC. Hepatocellular carcinoma: current management and recent advances. Hepatobiliary Pancreat Dis Int. 2008;7:237–57.PubMed
5.
Zurück zum Zitat Patel SR, Dressler GR. BMP7 signaling in renal development and disease. Trends Mol Med. 2005;11:512–8.PubMedCrossRef Patel SR, Dressler GR. BMP7 signaling in renal development and disease. Trends Mol Med. 2005;11:512–8.PubMedCrossRef
9.
Zurück zum Zitat Buijs JT, Rentsch CA, van der Horst G, van Overveld PG, Wetterwald A, Schwaninger R, Henriquez NV, Ten Dijke P, Borovecki F, Markwalder R, Thalmann GN, Papapoulos SE, Pelger RC, Vukicevic S, Cecchini MG, Löwik CW, van der Pluijm G. BMP7, a putative regulator of epithelial homeostasis in the human prostate, is a potent inhibitor of prostate cancer bone metastasis in vivo. Am J Pathol. 2007;171:1047–57. doi:10.2353/ajpath.2007.070168.PubMedCrossRef Buijs JT, Rentsch CA, van der Horst G, van Overveld PG, Wetterwald A, Schwaninger R, Henriquez NV, Ten Dijke P, Borovecki F, Markwalder R, Thalmann GN, Papapoulos SE, Pelger RC, Vukicevic S, Cecchini MG, Löwik CW, van der Pluijm G. BMP7, a putative regulator of epithelial homeostasis in the human prostate, is a potent inhibitor of prostate cancer bone metastasis in vivo. Am J Pathol. 2007;171:1047–57. doi:10.​2353/​ajpath.​2007.​070168.PubMedCrossRef
10.
Zurück zum Zitat Zeisberg EM, Tarnavski O, Zeisberg M, Dorfman AL, McMullen JR, Gustafsson E, Chandraker A, Yuan X, Pu WT, Roberts AB, Neilson EG, Sayegh MH, Izumo S, Kalluri R. Endothelial-tomesenchymal transition contributes to cardiac fibrosis. Nature. 2007;13:952–61. doi:10.1038/nm1613.CrossRef Zeisberg EM, Tarnavski O, Zeisberg M, Dorfman AL, McMullen JR, Gustafsson E, Chandraker A, Yuan X, Pu WT, Roberts AB, Neilson EG, Sayegh MH, Izumo S, Kalluri R. Endothelial-tomesenchymal transition contributes to cardiac fibrosis. Nature. 2007;13:952–61. doi:10.​1038/​nm1613.CrossRef
11.
Zurück zum Zitat Alarmo EL, Rauta J, Kauraniemi P, Karhu R, Kuukasjärvi T, Kallioniemi A. Bone morphogenetic protein 7 is widely overexpressed in primary breast cancer. Genes Chromosomes Cancer. 2006;45:411–9. doi:10.1002/gcc.20307.PubMedCrossRef Alarmo EL, Rauta J, Kauraniemi P, Karhu R, Kuukasjärvi T, Kallioniemi A. Bone morphogenetic protein 7 is widely overexpressed in primary breast cancer. Genes Chromosomes Cancer. 2006;45:411–9. doi:10.​1002/​gcc.​20307.PubMedCrossRef
16.
Zurück zum Zitat Fang W, Li X, Jiang Q, Liu Z, Yang H, Wang S, Xie S, Liu Q, Liu T, Huang J, Xie W, Li Z, Zhao Y, Wang E, Marincola FM, Yao K. Transcriptional patterns, biomarkers and pathways characterizing nasopharyngeal carcinoma of Southern China. J Transl Med. 2008;6:32. doi:10.1186/1479-5876-6-32.PubMedCrossRef Fang W, Li X, Jiang Q, Liu Z, Yang H, Wang S, Xie S, Liu Q, Liu T, Huang J, Xie W, Li Z, Zhao Y, Wang E, Marincola FM, Yao K. Transcriptional patterns, biomarkers and pathways characterizing nasopharyngeal carcinoma of Southern China. J Transl Med. 2008;6:32. doi:10.​1186/​1479-5876-6-32.PubMedCrossRef
17.
Zurück zum Zitat Tu L, Liu Z, He X, He Y, Yang H, Jiang Q, Xie S, Xiao G, Li X, Yao K, Fang W. Over-expression of eukaryotic translation initiation factor 4 gamma 1 correlates with tumor progression and poor prognosis in nasopharyngeal carcinoma. Mol Cancer. 2010;9:78. doi:10.1186/1476-4598-9-78.PubMedCrossRef Tu L, Liu Z, He X, He Y, Yang H, Jiang Q, Xie S, Xiao G, Li X, Yao K, Fang W. Over-expression of eukaryotic translation initiation factor 4 gamma 1 correlates with tumor progression and poor prognosis in nasopharyngeal carcinoma. Mol Cancer. 2010;9:78. doi:10.​1186/​1476-4598-9-78.PubMedCrossRef
19.
Zurück zum Zitat Zhu X-D, Zhang J-B, Zhuang P-Y, Zhu H-G, Zhang W, Xiong Y-Q, Wei-Zhong Wu L, Wang Z-YT, Sun H-C. High expression of macrophage colony-stimulating factor in peritumoral liver tissue is associated with poor survival after curative resection of hepatocellular carcinoma. J Clin Oncol. 2008;26:2707–16. doi:10.1200/JCO.2007.15.6521.PubMedCrossRef Zhu X-D, Zhang J-B, Zhuang P-Y, Zhu H-G, Zhang W, Xiong Y-Q, Wei-Zhong Wu L, Wang Z-YT, Sun H-C. High expression of macrophage colony-stimulating factor in peritumoral liver tissue is associated with poor survival after curative resection of hepatocellular carcinoma. J Clin Oncol. 2008;26:2707–16. doi:10.​1200/​JCO.​2007.​15.​6521.PubMedCrossRef
20.
Zurück zum Zitat Kelly K, Crowley J, Bunn Jr PA, Presant CA, Grevstad PK, Moinpour CM, Ramsey SD, Wozniak AJ, Weiss GR, Moore DF, Israel VK, Livingston RB, Gandara DR. Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non-small-cell lung cancer: a Southwest Oncology Group trial. J Clin Oncol. 2001;19:3210–8.PubMed Kelly K, Crowley J, Bunn Jr PA, Presant CA, Grevstad PK, Moinpour CM, Ramsey SD, Wozniak AJ, Weiss GR, Moore DF, Israel VK, Livingston RB, Gandara DR. Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non-small-cell lung cancer: a Southwest Oncology Group trial. J Clin Oncol. 2001;19:3210–8.PubMed
21.
Zurück zum Zitat Hennessy BT, Hanrahan EO, Daly PA. Non-Hodgkin lymphoma: an update. Lancet Oncol. 2004;5:341–53.PubMedCrossRef Hennessy BT, Hanrahan EO, Daly PA. Non-Hodgkin lymphoma: an update. Lancet Oncol. 2004;5:341–53.PubMedCrossRef
22.
Zurück zum Zitat Peng SY, Lai PL, Chu JS, Lee PH, Tsung PT, Chen DS, Hsu HC. Expression and hypomethylation of alpha-fetoprotein gene in unicentric and multicentric human hepatocellular carcinomas. Hepatology. 1993;17:35–41.PubMedCrossRef Peng SY, Lai PL, Chu JS, Lee PH, Tsung PT, Chen DS, Hsu HC. Expression and hypomethylation of alpha-fetoprotein gene in unicentric and multicentric human hepatocellular carcinomas. Hepatology. 1993;17:35–41.PubMedCrossRef
23.
Zurück zum Zitat Hsu HC, Jeng YM, Mao TL, Chu JS, Lai PL, Peng SY. β-catenin mutations are associated with a subset of low stage hepatocellular carcinoma negative for hepatitis B virus and with favorable prognosis. Am J Pathol. 2000;157:763–70.PubMedCrossRef Hsu HC, Jeng YM, Mao TL, Chu JS, Lai PL, Peng SY. β-catenin mutations are associated with a subset of low stage hepatocellular carcinoma negative for hepatitis B virus and with favorable prognosis. Am J Pathol. 2000;157:763–70.PubMedCrossRef
26.
Zurück zum Zitat Hwang YH, Choi JY, Kim S, Chung ES, Kim T, Koh SS, Lee B, Bae SH, Kim J, Park YM. Over-expression of c-raf-1proto-oncogene in liver cirrhosis and hepatocellular carcinoma. Hepatol Res. 2004;29:113–21.PubMedCrossRef Hwang YH, Choi JY, Kim S, Chung ES, Kim T, Koh SS, Lee B, Bae SH, Kim J, Park YM. Over-expression of c-raf-1proto-oncogene in liver cirrhosis and hepatocellular carcinoma. Hepatol Res. 2004;29:113–21.PubMedCrossRef
Metadaten
Titel
Prognostic significance of BMP7 as an oncogene in hepatocellular carcinoma
verfasst von
Wei Li
Hong-Xin Cai
Xu-Ming Ge
Kai Li
Wei-Dong Xu
Wei-Hong Shi
Publikationsdatum
01.04.2013
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 2/2013
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-012-0594-x

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