Skip to main content
Top
Published in: Medical Oncology 8/2014

01-08-2014 | Original Paper

Combined detection of Gab1 and Gab2 expression predicts clinical outcome of patients with glioma

Authors: Hui Liu, Gang Li, Weitao Zeng, Pengxing Zhang, Feiyan Fan, Yanyang Tu, Yongsheng Zhang

Published in: Medical Oncology | Issue 8/2014

Login to get access

Abstract

Grb2-associated binder 1 (Gab1) and Gab2 play important roles in cancer cell signaling. In particular, it has been demonstrated that the upregulation of Gab2 may be correlated with the World Health Organization (WHO) grade of gliomas and that patients with high Gab2 expression levels exhibited shorter survival time. However, the prognostic value of combined expression of Gab1 and Gab2 has not been explored. Gab1 and Gab2 expression in human gliomas and non-neoplastic brain tissues was measured by immunohistochemistry. Both the expression levels of Gab1 and Gab2 proteins in glioma tissues were significantly higher than those in non-neoplastic brain tissues (both P < 0.001). In addition, the overexpression of Gab1 and Gab2 proteins were both significantly associated with advanced WHO grades (both P < 0.001) and low KPS (both P = 0.01). Moreover, the overall survival of patients with high Gab1 protein expression or high Gab2 protein expression was obviously lower than those with low expressions (both P < 0.001). Notably, glioma patients with combined overexpression of Gab1 and Gab2 proteins (Gab1-high/Gab2-high) had shortest overall survival (P < 0.001). Furthermore, multivariate analysis showed that Gab1 expression (P = 0.01), Gab2 expression (P = 0.02), and combined expression of Gab1 and Gab2 (Gab1/Gab2, P = 0.006) were all independent prognostic factors for overall survival in glioma patients. Gab1 and Gab2 proteins are differentially expressed in glioma patients and closely correlated with the biological behavior of this malignancy. Combination of Gab1 and Gab2 expression may represent a promising biomarker for prognostication of human gliomas.
Literature
1.
go back to reference Dunbar E, Yachnis AT. Glioma diagnosis: immunohistochemistry and beyond. Adv Anat Pathol. 2010;17:187–201.PubMedCrossRef Dunbar E, Yachnis AT. Glioma diagnosis: immunohistochemistry and beyond. Adv Anat Pathol. 2010;17:187–201.PubMedCrossRef
2.
go back to reference Zhang X, Yang H, Gong B, Jiang C, Yang L. Combined gene expression and protein interaction analysis of dynamic modularity in glioma prognosis. J Neurooncol. 2012;107:281–8.PubMedCrossRef Zhang X, Yang H, Gong B, Jiang C, Yang L. Combined gene expression and protein interaction analysis of dynamic modularity in glioma prognosis. J Neurooncol. 2012;107:281–8.PubMedCrossRef
3.
go back to reference Chu SH, Ma YB, Feng DF, Zhang H, Zhu ZA, Li ZQ, Jiang PC. Correlation of low SLC22A18 expression with poor prognosis in patients with glioma. J Clin Neurosci. 2012;19:95–8.PubMedCrossRef Chu SH, Ma YB, Feng DF, Zhang H, Zhu ZA, Li ZQ, Jiang PC. Correlation of low SLC22A18 expression with poor prognosis in patients with glioma. J Clin Neurosci. 2012;19:95–8.PubMedCrossRef
4.
go back to reference Johnson DR, Galanis E. Incorporation of prognostic and predictive factors into glioma clinical trials. Curr Oncol Rep. 2013;15:56–63.PubMedCrossRef Johnson DR, Galanis E. Incorporation of prognostic and predictive factors into glioma clinical trials. Curr Oncol Rep. 2013;15:56–63.PubMedCrossRef
5.
go back to reference Curran WJ Jr, Scott CB. Radiosurgery for glioma patients: hope or hype? Int J Radiat Oncol Biol Phys. 1996;36:1279–80.PubMedCrossRef Curran WJ Jr, Scott CB. Radiosurgery for glioma patients: hope or hype? Int J Radiat Oncol Biol Phys. 1996;36:1279–80.PubMedCrossRef
6.
go back to reference Vaughan TY, Verma S, Bunting KD. Grb2-associated binding (Gab) proteins in hematopoietic and immune cell biology. Am J Blood Res. 2011;1:130–4.PubMedCentralPubMed Vaughan TY, Verma S, Bunting KD. Grb2-associated binding (Gab) proteins in hematopoietic and immune cell biology. Am J Blood Res. 2011;1:130–4.PubMedCentralPubMed
7.
go back to reference Nishida K, Hirano T. The role of Gab family scaffolding adapter proteins in the signal transduction of cytokine and growth factor receptors. Cancer Sci. 2003;94:1029–33.PubMedCrossRef Nishida K, Hirano T. The role of Gab family scaffolding adapter proteins in the signal transduction of cytokine and growth factor receptors. Cancer Sci. 2003;94:1029–33.PubMedCrossRef
9.
go back to reference Hibi M, Hirano T. Gab-family adapter molecules in signal transduction of cytokine and growth factor receptors, and T and B cell antigen receptors. Leuk Lymphoma. 2000;37:299–307.PubMed Hibi M, Hirano T. Gab-family adapter molecules in signal transduction of cytokine and growth factor receptors, and T and B cell antigen receptors. Leuk Lymphoma. 2000;37:299–307.PubMed
10.
go back to reference Sarmay G, Angyal A, Kertesz A, Maus M, Medgyesi D. The multiple function of Grb2 associated binder (Gab) adaptor/scaffolding protein in immune cell signaling. Immunol Lett. 2006;104:76–82.PubMedCrossRef Sarmay G, Angyal A, Kertesz A, Maus M, Medgyesi D. The multiple function of Grb2 associated binder (Gab) adaptor/scaffolding protein in immune cell signaling. Immunol Lett. 2006;104:76–82.PubMedCrossRef
11.
go back to reference Lu Y, Xiong Y, Huo Y, Han J, Yang X, Zhang R, Zhu DS, Klein-Hessling S, Li J, Zhang X, Han X, Li Y, Shen B, He Y, Shibuya M, Feng GS, Luo J. Grb-2-associated binder 1 (Gab1) regulates postnatal ischemic and VEGF-induced angiogenesis through the protein kinase A endothelial NOS pathway. Proc Natl Acad Sci USA. 2011;108:2957–62.PubMedCentralPubMedCrossRef Lu Y, Xiong Y, Huo Y, Han J, Yang X, Zhang R, Zhu DS, Klein-Hessling S, Li J, Zhang X, Han X, Li Y, Shen B, He Y, Shibuya M, Feng GS, Luo J. Grb-2-associated binder 1 (Gab1) regulates postnatal ischemic and VEGF-induced angiogenesis through the protein kinase A endothelial NOS pathway. Proc Natl Acad Sci USA. 2011;108:2957–62.PubMedCentralPubMedCrossRef
12.
go back to reference Angyal A, Medgyesi D, Sarmay G. Grb2-associated binder 1 (Gab1) adaptor/scaffolding protein regulates Erk signal in human B cells. Ann NY Acad Sci. 2006;1090:326–31.PubMedCrossRef Angyal A, Medgyesi D, Sarmay G. Grb2-associated binder 1 (Gab1) adaptor/scaffolding protein regulates Erk signal in human B cells. Ann NY Acad Sci. 2006;1090:326–31.PubMedCrossRef
13.
go back to reference Shioyama W, Nakaoka Y, Higuchi K, Minami T, Taniyama Y, Nishida K, Kidoya H, Sonobe T, Naito H, Arita Y, Hashimoto T, Kuroda T, Fujio Y, Shirai M, Takakura N, Morishita R, Yamauchi-Takihara K, Kodama T, Hirano T, Mochizuki N, Komuro I. Docking protein Gab1 is an essential component of postnatal angiogenesis after ischemia via HGF/c-met signaling. Circ Res. 2011;108:664–75.PubMedCrossRef Shioyama W, Nakaoka Y, Higuchi K, Minami T, Taniyama Y, Nishida K, Kidoya H, Sonobe T, Naito H, Arita Y, Hashimoto T, Kuroda T, Fujio Y, Shirai M, Takakura N, Morishita R, Yamauchi-Takihara K, Kodama T, Hirano T, Mochizuki N, Komuro I. Docking protein Gab1 is an essential component of postnatal angiogenesis after ischemia via HGF/c-met signaling. Circ Res. 2011;108:664–75.PubMedCrossRef
14.
go back to reference Seiden-Long I, Navab R, Shih W, Li M, Chow J, Zhu CQ, Radulovich N, Saucier C, Tsao MS. Gab1 but not Grb2 mediates tumor progression in Met overexpressing colorectal cancer cells. Carcinogenesis. 2008;29:647–55.PubMedCrossRef Seiden-Long I, Navab R, Shih W, Li M, Chow J, Zhu CQ, Radulovich N, Saucier C, Tsao MS. Gab1 but not Grb2 mediates tumor progression in Met overexpressing colorectal cancer cells. Carcinogenesis. 2008;29:647–55.PubMedCrossRef
15.
16.
go back to reference Kapoor GS, Zhan Y, Johnson GR, O’Rourke DM. Distinct domains in the SHP-2 phosphatase differentially regulate epidermal growth factor receptor/NF-kappaB activation through Gab1 in glioblastoma cells. Mol Cell Biol. 2004;24:823–36.PubMedCentralPubMedCrossRef Kapoor GS, Zhan Y, Johnson GR, O’Rourke DM. Distinct domains in the SHP-2 phosphatase differentially regulate epidermal growth factor receptor/NF-kappaB activation through Gab1 in glioblastoma cells. Mol Cell Biol. 2004;24:823–36.PubMedCentralPubMedCrossRef
17.
go back to reference Gu H, Saito K, Klaman LD, Shen J, Fleming T, Wang Y, Pratt JC, Lin G, Lim B, Kinet JP, Neel BG. Essential role for Gab2 in the allergic response. Nature. 2001;412:186–90.PubMedCrossRef Gu H, Saito K, Klaman LD, Shen J, Fleming T, Wang Y, Pratt JC, Lin G, Lim B, Kinet JP, Neel BG. Essential role for Gab2 in the allergic response. Nature. 2001;412:186–90.PubMedCrossRef
18.
go back to reference Adams SJ, Aydin IT, Celebi JT. GAB2–a scaffolding protein in cancer. Mol Cancer Res. 2012;10:1265–70.PubMedCrossRef Adams SJ, Aydin IT, Celebi JT. GAB2–a scaffolding protein in cancer. Mol Cancer Res. 2012;10:1265–70.PubMedCrossRef
19.
go back to reference Bentires-Alj M, Gil SG, Chan R, Wang ZC, Wang Y, Imanaka N. A role for the scaffolding adapter GAB2 in breast cancer. Nat Med. 2006;12:114–21.PubMedCrossRef Bentires-Alj M, Gil SG, Chan R, Wang ZC, Wang Y, Imanaka N. A role for the scaffolding adapter GAB2 in breast cancer. Nat Med. 2006;12:114–21.PubMedCrossRef
20.
go back to reference Lee SH, Jeong EG, Nam SW, Lee JY, Yoo NJ. Increased expression of Gab2, a scaffolding adaptor of the tyrosine kinase signalling, in gastric carcinomas. Pathology. 2007;39:326–9.PubMedCrossRef Lee SH, Jeong EG, Nam SW, Lee JY, Yoo NJ. Increased expression of Gab2, a scaffolding adaptor of the tyrosine kinase signalling, in gastric carcinomas. Pathology. 2007;39:326–9.PubMedCrossRef
21.
go back to reference Chernoff KA, Bordone L, Horst B, Simon K, Twadell W, Lee K, Cohen JA, Wang S, Silvers DN, Brunner G, Celebi JT. GAB2 amplifications refine molecular classification of melanoma. Clin Cancer Res. 2009;15:4288–91.PubMedCentralPubMedCrossRef Chernoff KA, Bordone L, Horst B, Simon K, Twadell W, Lee K, Cohen JA, Wang S, Silvers DN, Brunner G, Celebi JT. GAB2 amplifications refine molecular classification of melanoma. Clin Cancer Res. 2009;15:4288–91.PubMedCentralPubMedCrossRef
22.
go back to reference Samanta A, Perazzona B, Chakraborty S, Sun X, Modi H, Bhatia R, Priebe W, Arlinghaus R. Janus kinase 2 regulates Bcr-Abl signaling in chronic myeloid leukemia. Leukemia. 2011;25:463–72.PubMedCentralPubMedCrossRef Samanta A, Perazzona B, Chakraborty S, Sun X, Modi H, Bhatia R, Priebe W, Arlinghaus R. Janus kinase 2 regulates Bcr-Abl signaling in chronic myeloid leukemia. Leukemia. 2011;25:463–72.PubMedCentralPubMedCrossRef
23.
go back to reference Brummer T, Schramek D, Hayes VM, Bennett HL, Caldon CE, Musgrove EA. Increased proliferation and altered growth factor dependency of human mammary epithelial cells overexpressing the Gab2 docking protein. J Biol Chem. 2005;281:626–37.PubMedCrossRef Brummer T, Schramek D, Hayes VM, Bennett HL, Caldon CE, Musgrove EA. Increased proliferation and altered growth factor dependency of human mammary epithelial cells overexpressing the Gab2 docking protein. J Biol Chem. 2005;281:626–37.PubMedCrossRef
24.
go back to reference Xu XL, Wang X, Chen ZL, Jin M, Yang W, Zhao GF, Li JW. Overexpression of Grb2-associated binder 2 in human lung cancer. Int J Biol Sci. 2011;7:496–504.PubMedCentralPubMedCrossRef Xu XL, Wang X, Chen ZL, Jin M, Yang W, Zhao GF, Li JW. Overexpression of Grb2-associated binder 2 in human lung cancer. Int J Biol Sci. 2011;7:496–504.PubMedCentralPubMedCrossRef
25.
go back to reference Shi L, Sun X, Zhang J, Zhao C, Li H, Liu Z, Fang C, Wang X, Zhao C, Zhang X, Zhou F, Lu S, Luo R, Zhang B. Gab2 expression in glioma and its implications for tumor invasion. Acta Oncol. 2013;52:1739–50.PubMedCrossRef Shi L, Sun X, Zhang J, Zhao C, Li H, Liu Z, Fang C, Wang X, Zhao C, Zhang X, Zhou F, Lu S, Luo R, Zhang B. Gab2 expression in glioma and its implications for tumor invasion. Acta Oncol. 2013;52:1739–50.PubMedCrossRef
26.
go back to reference Rodrigues GA, Falasca M, Zhang Z, Schlessinger J. A novel positive feedback loop mediated by the docking protein Gab1 and phosphatidylinositol 3-kinase in epidermal growth factor receptor signaling. Mol Cell Biol. 2000;20:1448–59.PubMedCentralPubMedCrossRef Rodrigues GA, Falasca M, Zhang Z, Schlessinger J. A novel positive feedback loop mediated by the docking protein Gab1 and phosphatidylinositol 3-kinase in epidermal growth factor receptor signaling. Mol Cell Biol. 2000;20:1448–59.PubMedCentralPubMedCrossRef
27.
go back to reference Eulenfeld R, Schaper F. A new mechanism for the regulation of Gab1 recruitment to the plasma membrane. J Cell Sci. 2009;122:55–64.PubMedCrossRef Eulenfeld R, Schaper F. A new mechanism for the regulation of Gab1 recruitment to the plasma membrane. J Cell Sci. 2009;122:55–64.PubMedCrossRef
28.
go back to reference Bocanegra M, Bergamaschi A. Kim YH, Miller MA, Rajput AB, Kao J et al. Focal amplification and oncogene dependency of GAB2 in breast cancer. Oncogene. 2010;29:774–9.PubMedCrossRef Bocanegra M, Bergamaschi A. Kim YH, Miller MA, Rajput AB, Kao J et al. Focal amplification and oncogene dependency of GAB2 in breast cancer. Oncogene. 2010;29:774–9.PubMedCrossRef
Metadata
Title
Combined detection of Gab1 and Gab2 expression predicts clinical outcome of patients with glioma
Authors
Hui Liu
Gang Li
Weitao Zeng
Pengxing Zhang
Feiyan Fan
Yanyang Tu
Yongsheng Zhang
Publication date
01-08-2014
Publisher
Springer US
Published in
Medical Oncology / Issue 8/2014
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-014-0077-6

Other articles of this Issue 8/2014

Medical Oncology 8/2014 Go to the issue