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Erschienen in: Medical Oncology 5/2014

01.05.2014 | Original Paper

Expression of cytoskeleton regulatory protein Mena in human hepatocellular carcinoma and its prognostic significance

verfasst von: Kunpeng Hu, Jiani Wang, Zhicheng Yao, Bo Liu, Yuan Lin, Lei Liu, Lihua Xu

Erschienen in: Medical Oncology | Ausgabe 5/2014

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Abstract

The molecular mechanisms of the development and progression of hepatocellular carcinoma (HCC) are poorly understood. The main objective of this study was to analyze the expression of Enabled [mammalian Ena (Mena)] protein and its clinical significance in human HCC. The Mena expression was examined at mRNA and protein levels by real-time quantitative polymerase chain reaction and Western blotting analysis in ten paired HCC tissues and the adjacent normal tissues. The expression of Mena protein in 81 specimens of HCC tissues was determined by immunohistochemistry. Associations of Mena expression with the clinicopathological features were analyzed, and prognosis of HCC patients was evaluated. The result shows the expression of Mena mRNA and protein was higher in HCC than in the adjacent normal tissues in ten paired samples. Mena was mainly accumulated in the cytoplasm of tumor cells and over-expressed in 40.74 % (33/81) patients by immunohistochemical staining. Over-expression of Mena was significantly associated with poor cellular differentiation (P = 0.025), advanced tumor stage (P = 0.003) and worse disease-free survival (DFS, P < 0.001). In addition, Mena is an independent prognostic factor for DFS in multivariate analysis (HR 2.309, 95 % CI 1.104–4.828; P = 0.026). Mena is up-regulated in HCC and associated with tumor differentiation and clinical stage. Mena may be an independent prognostic marker for DFS of HCC patients.
Literatur
1.
Zurück zum Zitat Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000. Int J Cancer. 2001;94(2):153–6.PubMedCrossRef Parkin DM, Bray F, Ferlay J, Pisani P. Estimating the world cancer burden: Globocan 2000. Int J Cancer. 2001;94(2):153–6.PubMedCrossRef
2.
Zurück zum Zitat Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ. Cancer statistics, 2005. CA Cancer J Clin. 2005;55(1):10–30.PubMedCrossRef Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ. Cancer statistics, 2005. CA Cancer J Clin. 2005;55(1):10–30.PubMedCrossRef
3.
Zurück zum Zitat Yu MC, Yuan JM. Environmental factors and risk for hepatocellular carcinoma. Gastroenterology. 2004;127(5 Suppl 1):S72–8.PubMedCrossRef Yu MC, Yuan JM. Environmental factors and risk for hepatocellular carcinoma. Gastroenterology. 2004;127(5 Suppl 1):S72–8.PubMedCrossRef
4.
Zurück zum Zitat Pisani P, Parkin DM, Bray F, Ferlay J. Estimates of the worldwide mortality from 25 cancers in 1990. Int J Cancer. 1999;83(1):18–29.PubMedCrossRef Pisani P, Parkin DM, Bray F, Ferlay J. Estimates of the worldwide mortality from 25 cancers in 1990. Int J Cancer. 1999;83(1):18–29.PubMedCrossRef
6.
Zurück zum Zitat Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007;57(1):43–66.PubMedCrossRef Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007;57(1):43–66.PubMedCrossRef
7.
Zurück zum Zitat El-Serag HB, Mason AC. Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med. 1999;340(10):745–50.PubMedCrossRef El-Serag HB, Mason AC. Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med. 1999;340(10):745–50.PubMedCrossRef
8.
Zurück zum Zitat El-Serag HB, Lau M, Eschbach K, Davila J, Goodwin J. Epidemiology of hepatocellular carcinoma in Hispanics in the United States. Arch Intern Med. 2007;167(18):1983–9.PubMedCrossRef El-Serag HB, Lau M, Eschbach K, Davila J, Goodwin J. Epidemiology of hepatocellular carcinoma in Hispanics in the United States. Arch Intern Med. 2007;167(18):1983–9.PubMedCrossRef
9.
Zurück zum Zitat Huitzil-Melendez FD, Capanu M, O’Reilly EM, Duffy A, Gansukh B, Saltz LL, Abou-Alfa GK. Advanced hepatocellular carcinoma: which staging systems best predict prognosis? J Clin Oncol. 2010;28(17):2889–95.PubMedCentralPubMedCrossRef Huitzil-Melendez FD, Capanu M, O’Reilly EM, Duffy A, Gansukh B, Saltz LL, Abou-Alfa GK. Advanced hepatocellular carcinoma: which staging systems best predict prognosis? J Clin Oncol. 2010;28(17):2889–95.PubMedCentralPubMedCrossRef
10.
Zurück zum Zitat Di Modugno F, Bronzi G, Scanlan MJ, Del Bello D, Cascioli S, Venturo I, Botti C, Nicotra MR, Mottolese M, Natali PG, et al. Human Mena protein, a serex-defined antigen overexpressed in breast cancer eliciting both humoral and CD8 + T-cell immune response. Int J Cancer. 2004;109(6):909–18.PubMedCrossRef Di Modugno F, Bronzi G, Scanlan MJ, Del Bello D, Cascioli S, Venturo I, Botti C, Nicotra MR, Mottolese M, Natali PG, et al. Human Mena protein, a serex-defined antigen overexpressed in breast cancer eliciting both humoral and CD8 + T-cell immune response. Int J Cancer. 2004;109(6):909–18.PubMedCrossRef
11.
Zurück zum Zitat Bear JE, Svitkina TM, Krause M, Schafer DA, Loureiro JJ, Strasser GA, Maly IV, Chaga OY, Cooper JA, Borisy GG, et al. Antagonism between Ena/VASP proteins and actin filament capping regulates fibroblast motility. Cell. 2002;109(4):509–21.PubMedCrossRef Bear JE, Svitkina TM, Krause M, Schafer DA, Loureiro JJ, Strasser GA, Maly IV, Chaga OY, Cooper JA, Borisy GG, et al. Antagonism between Ena/VASP proteins and actin filament capping regulates fibroblast motility. Cell. 2002;109(4):509–21.PubMedCrossRef
12.
Zurück zum Zitat Barzik M, Kotova TI, Higgs HN, Hazelwood L, Hanein D, Gertler FB, Schafer DA. Ena/VASP proteins enhance actin polymerization in the presence of barbed end capping proteins. J Biol Chem. 2005;280(31):28653–62.PubMedCentralPubMedCrossRef Barzik M, Kotova TI, Higgs HN, Hazelwood L, Hanein D, Gertler FB, Schafer DA. Ena/VASP proteins enhance actin polymerization in the presence of barbed end capping proteins. J Biol Chem. 2005;280(31):28653–62.PubMedCentralPubMedCrossRef
13.
Zurück zum Zitat Pino MS, Balsamo M, Di Modugno F, Mottolese M, Alessio M, Melucci E, Milella M, McConkey DJ, Philippar U, Gertler FB, et al. Human Mena + 11a isoform serves as a marker of epithelial phenotype and sensitivity to epidermal growth factor receptor inhibition in human pancreatic cancer cell lines. Clin Cancer Res. 2008;14(15):4943–50.PubMedCentralPubMedCrossRef Pino MS, Balsamo M, Di Modugno F, Mottolese M, Alessio M, Melucci E, Milella M, McConkey DJ, Philippar U, Gertler FB, et al. Human Mena + 11a isoform serves as a marker of epithelial phenotype and sensitivity to epidermal growth factor receptor inhibition in human pancreatic cancer cell lines. Clin Cancer Res. 2008;14(15):4943–50.PubMedCentralPubMedCrossRef
14.
Zurück zum Zitat Gurzu S, Jung I, Prantner I, Ember I, Pavai Z, Mezei T. The expression of cytoskeleton regulatory protein Mena in colorectal lesions. Rom J Morphol Embryol. 2008;49(3):345–9.PubMed Gurzu S, Jung I, Prantner I, Ember I, Pavai Z, Mezei T. The expression of cytoskeleton regulatory protein Mena in colorectal lesions. Rom J Morphol Embryol. 2008;49(3):345–9.PubMed
15.
Zurück zum Zitat Gurzu S, Jung I, Prantner I, Chira L, Ember I. The immunohistochemical aspects of protein Mena in cervical lesions. Rom J Morphol Embryol. 2009;50(2):213–6.PubMed Gurzu S, Jung I, Prantner I, Chira L, Ember I. The immunohistochemical aspects of protein Mena in cervical lesions. Rom J Morphol Embryol. 2009;50(2):213–6.PubMed
16.
Zurück zum Zitat Gurzu S, Krause M, Ember I, Azamfirei L, Gobel G, Feher K, Jung I. Mena, a new available marker in tumors of salivary glands? Eur J Histochem. 2012;56(1):e8.PubMedCentralPubMedCrossRef Gurzu S, Krause M, Ember I, Azamfirei L, Gobel G, Feher K, Jung I. Mena, a new available marker in tumors of salivary glands? Eur J Histochem. 2012;56(1):e8.PubMedCentralPubMedCrossRef
17.
Zurück zum Zitat Di Modugno F, Mottolese M, Di Benedetto A, Conidi A, Novelli F, Perracchio L, Venturo I, Botti C, Jager E, Santoni A, et al. The cytoskeleton regulatory protein hMena (ENAH) is overexpressed in human benign breast lesions with high risk of transformation and human epidermal growth factor receptor-2-positive/hormonal receptor-negative tumors. Clin Cancer Res. 2006;12(5):1470–8.PubMedCrossRef Di Modugno F, Mottolese M, Di Benedetto A, Conidi A, Novelli F, Perracchio L, Venturo I, Botti C, Jager E, Santoni A, et al. The cytoskeleton regulatory protein hMena (ENAH) is overexpressed in human benign breast lesions with high risk of transformation and human epidermal growth factor receptor-2-positive/hormonal receptor-negative tumors. Clin Cancer Res. 2006;12(5):1470–8.PubMedCrossRef
18.
Zurück zum Zitat Di Modugno F, DeMonte L, Balsamo M, Bronzi G, Nicotra MR, Alessio M, Jager E, Condeelis JS, Santoni A, Natali PG, et al. Molecular cloning of hMena (ENAH) and its splice variant hMena + 11a: epidermal growth factor increases their expression and stimulates hMena + 11a phosphorylation in breast cancer cell lines. Cancer Res. 2007;67(6):2657–65.PubMedCentralPubMedCrossRef Di Modugno F, DeMonte L, Balsamo M, Bronzi G, Nicotra MR, Alessio M, Jager E, Condeelis JS, Santoni A, Natali PG, et al. Molecular cloning of hMena (ENAH) and its splice variant hMena + 11a: epidermal growth factor increases their expression and stimulates hMena + 11a phosphorylation in breast cancer cell lines. Cancer Res. 2007;67(6):2657–65.PubMedCentralPubMedCrossRef
19.
Zurück zum Zitat Shah SA, Cleary SP, Wei AC, Yang I, Taylor BR, Hemming AW, Langer B, Grant DR, Greig PD, Gallinger S. Recurrence after liver resection for hepatocellular carcinoma: risk factors, treatment, and outcomes. Surgery. 2007;141(3):330–9.PubMedCrossRef Shah SA, Cleary SP, Wei AC, Yang I, Taylor BR, Hemming AW, Langer B, Grant DR, Greig PD, Gallinger S. Recurrence after liver resection for hepatocellular carcinoma: risk factors, treatment, and outcomes. Surgery. 2007;141(3):330–9.PubMedCrossRef
20.
Zurück zum Zitat Rao J, Li N. Microfilament actin remodeling as a potential target for cancer drug development. Curr Cancer Drug Targets. 2004;4(4):345–54.PubMedCrossRef Rao J, Li N. Microfilament actin remodeling as a potential target for cancer drug development. Curr Cancer Drug Targets. 2004;4(4):345–54.PubMedCrossRef
21.
Zurück zum Zitat Kojiro M, Nakashima O. Histopathologic evaluation of hepatocellular carcinoma with special reference to small early stage tumors. Semin Liver Dis. 1999;19(3):287–96.PubMedCrossRef Kojiro M, Nakashima O. Histopathologic evaluation of hepatocellular carcinoma with special reference to small early stage tumors. Semin Liver Dis. 1999;19(3):287–96.PubMedCrossRef
22.
Zurück zum Zitat Xu MZ, Yao TJ, Lee NP, Ng IO, Chan YT, Zender L, Lowe SW, Poon RT, Luk JM. Yes-associated protein is an independent prognostic marker in hepatocellular carcinoma. Cancer. 2009;115(19):4576–85.PubMedCentralPubMedCrossRef Xu MZ, Yao TJ, Lee NP, Ng IO, Chan YT, Zender L, Lowe SW, Poon RT, Luk JM. Yes-associated protein is an independent prognostic marker in hepatocellular carcinoma. Cancer. 2009;115(19):4576–85.PubMedCentralPubMedCrossRef
Metadaten
Titel
Expression of cytoskeleton regulatory protein Mena in human hepatocellular carcinoma and its prognostic significance
verfasst von
Kunpeng Hu
Jiani Wang
Zhicheng Yao
Bo Liu
Yuan Lin
Lei Liu
Lihua Xu
Publikationsdatum
01.05.2014
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 5/2014
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-014-0939-y

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