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Published in: BMC Cancer 1/2021

Open Access 01-12-2021 | Metastasis | Research article

Expression of BAG1 is associated with prognosis in kidney renal clear cell carcinoma based on bioinformatics

Authors: Hongrong Wu, Minjing Liu, Yuejun He, Guozhao Meng, Wanbei Guo, Qiong Guo

Published in: BMC Cancer | Issue 1/2021

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Abstract

Background

BCL2 associated Athano-Gene 1 (BAG1) has been described to be involved in the development and progression of cancer. But the role of BAG1 in kidney renal clear cell carcinoma (KIRC) has remained largely unknown.

Methods

We performed bioinformatic analysis of data from TCGA and GEO dataset. The role of BAG1 in KIRC was explored by Logistic and Cox regression model. The molecular mechanisms of BAG1 was revealed by GSEA.

Results

The current study found that the KIRC tumor samples have a low level of BAG1 mRNA expression compared to the matched normal tissues based on TCGA data and GEO databases. Low expression of BAG1 in KIRC was significantly associated with Sex, clinical pathological stage, tumor-node-metastasis (TNM) stage, hemoglobin levels, cancer status and history of neoadjuvant treatment. Kaplan-Meier survival analysis indicated that KIRC patients with BAG1 high expression have a longer survival time than those with BAG1 low expression (p < 0.000). Cox regression analysis showed that BAG1 remained independently associated with overall survival, with a hazard ratio (HR) of 1.75(CI:1.05–2.90; p = 0.029). GSEA indicated that the signaling pathways including fatty acid metabolism and oxidative phosphorylation were differentially enriched in high BAG1 expression phenotype.

Conclusions

These findings suggested that BAG1 expression may act as a potential favorable prognostic marker and challenging therapeutic target.
Literature
1.
go back to reference Wei EY, Hsieh JJ. A river model to map convergent cancer evolution and guide therapy in RCC. Nat Rev Urol. 2015;12:706.CrossRef Wei EY, Hsieh JJ. A river model to map convergent cancer evolution and guide therapy in RCC. Nat Rev Urol. 2015;12:706.CrossRef
2.
go back to reference Funakoshi T, Lee C-H, Hsieh JJ. A systematic review of predictive and prognostic biomarkers for VEGF-targeted therapy in renal cell carcinoma. Cancer Treat Rev. 2014;40:533–47.CrossRef Funakoshi T, Lee C-H, Hsieh JJ. A systematic review of predictive and prognostic biomarkers for VEGF-targeted therapy in renal cell carcinoma. Cancer Treat Rev. 2014;40:533–47.CrossRef
3.
go back to reference Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon Alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007;356:115–24.CrossRef Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon Alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007;356:115–24.CrossRef
4.
go back to reference Escudier B, Pluzanska A, Koralewski P, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet. 2007;370:2103–11.CrossRef Escudier B, Pluzanska A, Koralewski P, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet. 2007;370:2103–11.CrossRef
5.
go back to reference Takayama S, Sato T, Krajewski S, et al. Cloning and functional analysis of BAG-1: a novel Bcl-2-binding protein with anti-cell death activity. Cell. 1995;80:279–84.CrossRef Takayama S, Sato T, Krajewski S, et al. Cloning and functional analysis of BAG-1: a novel Bcl-2-binding protein with anti-cell death activity. Cell. 1995;80:279–84.CrossRef
6.
go back to reference Papadakis ES, Reeves T, Robson NH, Maishman T, Packham G, Cutress RI. BAG-1 as a biomarker in early breast cancer prognosis: a systematic review with meta-analyses. Br J Cancer. 2017;116:1585.CrossRef Papadakis ES, Reeves T, Robson NH, Maishman T, Packham G, Cutress RI. BAG-1 as a biomarker in early breast cancer prognosis: a systematic review with meta-analyses. Br J Cancer. 2017;116:1585.CrossRef
7.
go back to reference Cutress RI, Townsend PA, Brimmell M, Bateman AC, Hague A, Packham G. BAG-1 expression and function in human cancer. Br J Cancer. 2002;87:834.CrossRef Cutress RI, Townsend PA, Brimmell M, Bateman AC, Hague A, Packham G. BAG-1 expression and function in human cancer. Br J Cancer. 2002;87:834.CrossRef
8.
go back to reference Townsend PA, Dublin E, Hart IR, et al. BAG-i expression in human breast cancer: interrelationship between BAG-1 RNA, protein, HSC70 expression and clinico-pathological data. J Pathol. 2002;197:51–9.CrossRef Townsend PA, Dublin E, Hart IR, et al. BAG-i expression in human breast cancer: interrelationship between BAG-1 RNA, protein, HSC70 expression and clinico-pathological data. J Pathol. 2002;197:51–9.CrossRef
9.
go back to reference Southern SL, Collard TJ, Urban BC, et al. BAG-1 interacts with the p50–p50 homodimeric NF-κB complex: implications for colorectal carcinogenesis. Oncogene. 2011;31:2761.CrossRef Southern SL, Collard TJ, Urban BC, et al. BAG-1 interacts with the p50–p50 homodimeric NF-κB complex: implications for colorectal carcinogenesis. Oncogene. 2011;31:2761.CrossRef
10.
go back to reference Liu S, Ren B, Gao H, et al. Over-expression of BAG-1 in head and neck squamous cell carcinomas (HNSCC) is associated with cisplatin-resistance. J Transl Med. 2017;15:189.CrossRef Liu S, Ren B, Gao H, et al. Over-expression of BAG-1 in head and neck squamous cell carcinomas (HNSCC) is associated with cisplatin-resistance. J Transl Med. 2017;15:189.CrossRef
11.
go back to reference Davidson B, Valborg Reinertsen K, Trinh D, Reed W, Bohler PJ. BAG-1/SODD, HSP70, and HSP90 are potential prognostic markers of poor survival in node-negative breast carcinoma. Hum Pathol. 2016;54:64–73.CrossRef Davidson B, Valborg Reinertsen K, Trinh D, Reed W, Bohler PJ. BAG-1/SODD, HSP70, and HSP90 are potential prognostic markers of poor survival in node-negative breast carcinoma. Hum Pathol. 2016;54:64–73.CrossRef
12.
go back to reference Kruppa J, Jung K. Automated multigroup outlier identification in molecular high-throughput data using bagplots and gemplots. BMC Bioinformatics. 2017;18:232.CrossRef Kruppa J, Jung K. Automated multigroup outlier identification in molecular high-throughput data using bagplots and gemplots. BMC Bioinformatics. 2017;18:232.CrossRef
13.
go back to reference Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45:W98–w102.CrossRef Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45:W98–w102.CrossRef
14.
go back to reference Subramanian A, Tamayo P, Mootha VK, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci. 2005;102:15545–50.CrossRef Subramanian A, Tamayo P, Mootha VK, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci. 2005;102:15545–50.CrossRef
15.
go back to reference Wu H, Zhang J. Decreased expression of TFAP2B in endometrial cancer predicts poor prognosis: a study based on TCGA data. Gynecol Oncol. 2018;149:592–7.CrossRef Wu H, Zhang J. Decreased expression of TFAP2B in endometrial cancer predicts poor prognosis: a study based on TCGA data. Gynecol Oncol. 2018;149:592–7.CrossRef
16.
go back to reference Huang B, Zhou H, Lang X, Liu Z, Xiong F, Wang S. Expression of BAG-1 is closely related to cell differentiation and TNM stage in esophageal cancer and its downregulation inhibits the proliferation and invasion of human esophageal carcinoma cells. Oncol Rep. 2014;32:1441–6.CrossRef Huang B, Zhou H, Lang X, Liu Z, Xiong F, Wang S. Expression of BAG-1 is closely related to cell differentiation and TNM stage in esophageal cancer and its downregulation inhibits the proliferation and invasion of human esophageal carcinoma cells. Oncol Rep. 2014;32:1441–6.CrossRef
17.
go back to reference Yang J, Cai Z, Du W, Li J, Chen T, Xu Y. The relationship between bag-1 and gastric cancer clinicopathologic characteristic. Chin-Ger J Clin Oncol. 2011;10:459.CrossRef Yang J, Cai Z, Du W, Li J, Chen T, Xu Y. The relationship between bag-1 and gastric cancer clinicopathologic characteristic. Chin-Ger J Clin Oncol. 2011;10:459.CrossRef
18.
go back to reference Jodoin R, Perreault J-P, Bisaillon M. Abstract A08: A 5′UTR RNA G-Quadruplex structure affects both the cap-dependent and independent translation of BAG-1, an mRNA involved in colorectal cancer. AACR; 2017. Jodoin R, Perreault J-P, Bisaillon M. Abstract A08: A 5′UTR RNA G-Quadruplex structure affects both the cap-dependent and independent translation of BAG-1, an mRNA involved in colorectal cancer. AACR; 2017.
19.
go back to reference Shen Z, Li Y, Zhao C, Wang F. Zhou R and Chen G: miR-494-BAG-1 axis is involved in cinobufacini-induced cell proliferation and apoptosis in gastric cancer. Mol Med Rep. 2018;17:7435–41.PubMed Shen Z, Li Y, Zhao C, Wang F. Zhou R and Chen G: miR-494-BAG-1 axis is involved in cinobufacini-induced cell proliferation and apoptosis in gastric cancer. Mol Med Rep. 2018;17:7435–41.PubMed
20.
go back to reference Cato L, Neeb A, Sharp A, et al. Development of bag-1L as a therapeutic target in androgen receptor-dependent prostate cancer. Elife. 2017;6:e27159.CrossRef Cato L, Neeb A, Sharp A, et al. Development of bag-1L as a therapeutic target in androgen receptor-dependent prostate cancer. Elife. 2017;6:e27159.CrossRef
21.
go back to reference Galvan V, Brandimarti R, Munger J, Roizman B. Bcl-2 blocks a caspase-dependent pathway of apoptosis activated by herpes simplex virus 1 infection in HEp-2 cells. J Virol. 2000;74:1931–8.CrossRef Galvan V, Brandimarti R, Munger J, Roizman B. Bcl-2 blocks a caspase-dependent pathway of apoptosis activated by herpes simplex virus 1 infection in HEp-2 cells. J Virol. 2000;74:1931–8.CrossRef
22.
go back to reference Wang HG, Takayama S, Rapp UR, Reed JC. Bcl-2 interacting protein, BAG-1, binds to and activates the kinase Raf-1. Proc Natl Acad Sci U S A. 1996;93:7063–8.CrossRef Wang HG, Takayama S, Rapp UR, Reed JC. Bcl-2 interacting protein, BAG-1, binds to and activates the kinase Raf-1. Proc Natl Acad Sci U S A. 1996;93:7063–8.CrossRef
23.
go back to reference van der Zee JA, Ten Hagen TL, Hop WC, et al. Bcl-2 associated anthanogen-1 (Bag-1) expression and prognostic value in pancreatic head and periampullary cancer. Eur J Cancer. 2013;49:323–8.CrossRef van der Zee JA, Ten Hagen TL, Hop WC, et al. Bcl-2 associated anthanogen-1 (Bag-1) expression and prognostic value in pancreatic head and periampullary cancer. Eur J Cancer. 2013;49:323–8.CrossRef
24.
go back to reference Ni W, Chen B, Zhou G, et al. Overexpressed nuclear BAG-1 in human hepatocellular carcinoma is associated with poor prognosis and resistance to doxorubicin. J Cell Biochem. 2013;114:2120–30.CrossRef Ni W, Chen B, Zhou G, et al. Overexpressed nuclear BAG-1 in human hepatocellular carcinoma is associated with poor prognosis and resistance to doxorubicin. J Cell Biochem. 2013;114:2120–30.CrossRef
25.
go back to reference Liberman EA, Topaly VP, Tsofina LM, Jasaitis AA, Skulachev VP. Mechanism of coupling of oxidative phosphorylation and the membrane potential of mitochondria. Nature. 1969;222:1076–8.CrossRef Liberman EA, Topaly VP, Tsofina LM, Jasaitis AA, Skulachev VP. Mechanism of coupling of oxidative phosphorylation and the membrane potential of mitochondria. Nature. 1969;222:1076–8.CrossRef
26.
go back to reference Xu, Jing, Nie, et al. Down-regulated energy metabolism genes associated with mitochondria oxidative phosphorylation and fatty acid metabolism in viral cardiomyopathy mouse heart. Mol Biol Rep. 2011;38:4007–13.CrossRef Xu, Jing, Nie, et al. Down-regulated energy metabolism genes associated with mitochondria oxidative phosphorylation and fatty acid metabolism in viral cardiomyopathy mouse heart. Mol Biol Rep. 2011;38:4007–13.CrossRef
Metadata
Title
Expression of BAG1 is associated with prognosis in kidney renal clear cell carcinoma based on bioinformatics
Authors
Hongrong Wu
Minjing Liu
Yuejun He
Guozhao Meng
Wanbei Guo
Qiong Guo
Publication date
01-12-2021
Publisher
BioMed Central
Keyword
Metastasis
Published in
BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-021-07874-w

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