The Association Between Gelsolin-like Actin-capping Protein (CapG) Overexpression and Bladder Cancer Prognosis
1 January 2020
Purpose: Muscle-invasive bladder cancer (MIBC) is associated with disease progression and metastasis leading to poor prognosis. Current chemotherapy approaches have not adequately increased patient survival. Therefore, in this study, tissue proteome of patients with MIBC was performed to introduce possible protein candidates for bladder cancer prognosis as well as targeted therapy.
Materials and Methods: The tumoral and normal adjacent bladder tissues were obtained from patients diagnosed with bladder cancer. Two-dimensional gel electrophoresis (2-DE) and liquid chromatography-mass spectrometry (LC-MS/MS) were used to analyze tissue proteome. CAPG protein was further examined using Real-time PCR and western blot analysis.
Results: The 2-DE analysis and LC-MS/MS identified Gelsolin-like Actin-capping (CAPG) protein as differentially expressed protein in tumor tissues of bladder cancer compared with normal adjacent tissues. Western blot analysis showed the CAPG overexpression in tumor tissues compared with normal adjacent tissues in a stage-dependent manner. Correspondingly, Real- time PCR showed a higher mRNA expression in tumoral bladder tissues than normal adjacent ones. CAPG mRNA overexpression had significantly a positive relation with tumor size (p = 0.019), the TNM staging (p = 0.001), and tumor differentiation (grade) (p = 0.006). Patients with lower levels of CAPG had higher recurrence-free survival in comparison with patients with higher level of CAPG (p = .027).
Conclusion: CAPG overexpression was correlated with size, stage, grade, and shorter time to recurrence of tumor. Therefore, CAPG overexpression could be related to poor prognosis of bladder cancer. These results suggest that CAPG may be considered as a prognostic factor and also for targeted therapy in bladder cancer.
- bladder cancer
- targeted therapy
How to Cite
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA: A Cancer Journal for Clinicians. 2017;67:7-30.
Scosyrev E, Noyes K, Feng C, Messing E. Sex and racial differences in bladder cancer presentation and mortality in the US. Cancer. 2009;115:68-74.
Yang Z, Liu A, Xiong Q, et al. Prognostic value of differentially methylated gene profiles in bladder cancer. Journal of Cellular Physiology. 2019.
Usuba W, Urabe F, Yamamoto Y, et al. Circulating miRNA panels for specific and early detection in bladder cancer. Cancer science. 2019;110:408.
Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Annals of surgical oncology. 2010;17:1471-4.
Zhou Y, Song R, Ma C, et al. Discovery and validation of potential urinary biomarkers for bladder cancer diagnosis using a pseudotargeted GC-MS metabolomics method. Oncotarget. 2017;8:20719.
Kaufman DS, Shipley WU, Feldman AS. Bladder cancer. The Lancet. 2009;374:239-49.
Wallerand H, Bernhard J-C, Culine S, et al. Targeted therapies in non-muscle-invasive bladder cancer according to the signaling pathways. Paper presented at: Urologic Oncology: Seminars and Original Investigations, 2011.
Stein JP, Lieskovsky G, Cote R, et al. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. Journal of Clinical Oncology. 2001;19:666-75.
Kopsiaftis S, Phoenix KN, Sullivan KL, Hegde P, Taylor JA, Claffey KP. Role of AMPKalpha isoforms in bladder tumorigenesis. Cancer Research. 2013;73:310.
Zeng Z, Zhou W, Duan L, et al. Circular RNA circ‐VANGL1 as a competing endogenous RNA contributes to bladder cancer progression by regulating miR‐605‐3p/VANGL1 pathway. Journal of cellular physiology. 2019;234:3887-96.
Guo T, Kouvonen P, Koh CC, et al. Rapid mass spectrometric conversion of tissue biopsy samples into permanent quantitative digital proteome maps. Nature medicine. 2015;21:407.
Chen C-L, Chung T, Wu C-C. Comparative tissue proteomics of microdissected specimens reveals novel candidate biomarkers of bladder cancer. Molecular & cellular proteomics. 2015;14:2466-78.
Peng X, Gong F, Chen Y, et al. Proteomics identification of PGAM1 as a potential therapeutic target for urothelial bladder cancer. Journal of proteomics. 2016;132:85-92.
Oezdemir RF, Gaisa NT, Lindemann-Docter K, et al. Proteomic tissue profiling for the improvement of grading of noninvasive papillary urothelial neoplasia. Clinical biochemistry. 2012;45:7-11.
Niu H, Jiang H, Cheng B, et al. Stromal proteome expression profile and muscle-invasive bladder cancer research. Cancer cell international. 2012;12:39.
Røtterud R, Malmström P-U, Wahlqvist R, Tasken KA. The star chart to Ta bladder cancer: an unsophisticated analysis of two-dimensional gel electrophoresis proteome maps. Scandinavian journal of urology and nephrology. 2010;44:76-83.
Li J, Abraham S, Cheng L, et al. Proteomic‐based approach for biomarkers discovery in early detection of invasive urothelial carcinoma. PROTEOMICS–Clinical Applications. 2008;2:78-89.
Liu PF, Cao YW, Jiang HP, et al. Heterogeneity research in muscle-invasive bladder cancer based on differential protein expression analysis. Medical oncology. 2014;31:21.
Niu HT, Zhang YB, Jiang HP, et al. Differences in shotgun protein expression profile between superficial bladder transitional cell carcinoma and normal urothelium. Paper presented at: Urologic Oncology: Seminars and Original Investigations, 2009.
Knowles MA, Williamson M. Mutation of H-ras is infrequent in bladder cancer: confirmation by single-strand conformation polymorphism analysis, designed restriction fragment length polymorphisms, and direct sequencing. Cancer research. 1993;53:133-9.
Saito S, Hata M, Fukuyama R, et al. Screening of H‐ras Gene Point Mutations in 50 Cases of Bladder Carcinoma. International journal of urology. 1997;4:178-85.
Czerniak B, Cohen GL, Etkind P. Concurrent mutations of coding and regulatory sequences of the Ha-ras gene in urinary bladder carcinomas. Human pathology. 1992;23:1199-204.
Cheng L, Neumann R, Nehra A, Spotts B, Weaver A, Bostwick D. Cancer heterogeneity and its biologic implications in the grading of urothelial carcinoma. Cancer. 2000;88:1663-70.
Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical biochemistry. 1976;72:248-54.
Candiano G, Bruschi M, Musante L. Blue silver: a very sensitive colloidal Coomassie G‐250 staining for proteome analysis. Electrophoresis. 2004;25:1327-33.
Shannon P, Markiel A, Ozier O, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome research. 2003;13:2498-504.
Assenov Y, Ramírez F, Schelhorn S-E, Lengauer T, Albrecht M. Computing topological parameters of biological networks. Bioinformatics. 2007;24:282-4.
Gheysarzadeh A, Sadeghifard N, Afraidooni L, et al. Serum-based microRNA biomarkers for major depression: MiR-16, miR-135a, and miR-1202. Journal of research in medical sciences: the official journal of Isfahan University of Medical Sciences. 2018;23.
Wang L, Chen S, Luo Y, et al. Identification of several cell cycle relevant genes highly correlated with the progression and prognosis of human bladder urothelial tumor. Journal of cellular physiology. 2019.
Song G, Ouyang G, Bao S. The activation of Akt/PKB signaling pathway and cell survival. Journal of cellular and molecular medicine. 2005;9:59-71.
Lei T, Zhao X, Jin S, Meng Q, Zhou H, Zhang M. Discovery of potential bladder cancer biomarkers by comparative urine proteomics and analysis. Clinical genitourinary cancer. 2013;11:56-62.
Li C, Li H, Zhang T, Li J, Liu L, Chang J. Discovery of Apo-A1 as a potential bladder cancer biomarker by urine proteomics and analysis. Biochemical and biophysical research communications. 2014;446:1047-52.
Hempel N, M Carrico P, Melendez JA. Manganese superoxide dismutase (Sod2) and redox-control of signaling events that drive metastasis. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents). 2011;11:191-201.
Lahat G, Zhu Q-S, Huang K-L. Vimentin is a novel anti-cancer therapeutic target; insights from in vitro and in vivo mice xenograft studies. PloS one. 2010;5:e10105.
Zhao J, Dong D, Sun L, Zhang G, Sun L. Prognostic significance of the epithelial-to-mesenchymal transition markers e-cadherin, vimentin and twist in bladder cancer. International braz j urol. 2014;40:179-89.
Ding X, Wang Y, Ma X. Expression of HMGA 2 in bladder cancer and its association with epithelial‐to‐mesenchymal transition. Cell proliferation. 2014;47:146-51.
Daly EB, Wind T, Jiang X-M, Sun L, Hogg PJ. Secretion of phosphoglycerate kinase from tumour cells is controlled by oxygen-sensing hydroxylases. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research. 2004;1691:17-22.
Tsai T-J, Chao W-Y, Chen C-C, Chen Y-J, Lin C-Y, Lee Y-R. Gelsolin-like Actin-capping Protein (CapG) Overexpression in the Cytoplasm of Human Hepatocellular Carcinoma, Associated with Cellular Invasion, Migration and Tumor Prognosis. Anticancer research. 2018;38:3943-50.
Tsai T-J, Lim Y-P, Chao W-Y, et al. Capping Actin Protein Overexpression in Human Colorectal Carcinoma and Its Contributed Tumor Migration. Analytical Cellular Pathology. 2018;2018.
Yun D-P, Wang Y-Q, Meng D-L, et al. Actin-capping protein CapG is associated with prognosis, proliferation and metastasis in human glioma. Oncology reports. 2018;39:1011-22.
Glaser J, Neumann M, Mei Q, et al. Macrophage capping protein CapG is a putative oncogene involved in migration and invasiveness in ovarian carcinoma. BioMed research international. 2014;2014.
Li B, Guo K, Li C. Influence of suppression of CapG gene expression by siRNA on the growth and metastasis of human prostate cancer cells. Genet Mol Res. 2015;14:15769-78.
Van Impe K, Bethuyne J, Cool S. A nanobody targeting the F-actin capping protein CapG restrains breast cancer metastasis. Breast cancer research. 2013;15:R116.
- Abstract Viewed: 167 times
- Just Accepted/5664 Downloaded: 54 times