BAG3 as a novel prognostic biomarker in kidney renal clear cell carcinoma correlating with immune infiltrates

Abstract Purpose BCL-2-associated athanogene 3 (BAG3) is an anti-apoptotic protein that plays an essential role in the onset and progression of multiple cancer types. However, the clinical significance of BAG3 in kidney renal clear cell carcinoma (KIRC) remains unclear. Methods Using Tumor IMmune Es...

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Main Authors: Binghao Gong, Yuan Huang, Zhenting Wang, Bangbei Wan, Yaohui Zeng, Cai Lv
Format: Article
Language:English
Published: BMC 2024-02-01
Series:European Journal of Medical Research
Subjects:
Online Access:https://doi.org/10.1186/s40001-024-01687-w
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author Binghao Gong
Yuan Huang
Zhenting Wang
Bangbei Wan
Yaohui Zeng
Cai Lv
author_facet Binghao Gong
Yuan Huang
Zhenting Wang
Bangbei Wan
Yaohui Zeng
Cai Lv
author_sort Binghao Gong
collection DOAJ
description Abstract Purpose BCL-2-associated athanogene 3 (BAG3) is an anti-apoptotic protein that plays an essential role in the onset and progression of multiple cancer types. However, the clinical significance of BAG3 in kidney renal clear cell carcinoma (KIRC) remains unclear. Methods Using Tumor IMmune Estimation Resource (TIMER), The Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) database, we explored the expression, prognostic value, and clinical correlations of BAG3 in KIRC. In addition, immunohistochemistry (IHC) of HKH cohort further validated the expression of BAG3 in KIRC and its impact on prognosis. Gene Set Cancer Analysis (GSCA) was utilized to scrutinize the prognostic value of BAG3 methylation. Gene Ontology (GO) term analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene set enrichment analysis (GSEA) were used to identify potential biological functions of BAG3 in KIRC. Single-sample gene set enrichment analysis (ssGSEA) was performed to confirm the correlation between BAG3 expression and immune cell infiltration. Results BAG3 mRNA expression and protein expression were significantly downregulated in KIRC tissues compared to normal kidney tissues, associated with adverse clinical–pathological factors and poor clinical prognosis. Multivariate Cox regression analysis indicated that low expression of BAG3 was an independent prognostic factor in KIRC patients. GSEA analysis showed that BAG3 is mainly involved in DNA methylation and the immune-related pathways in KIRC. In addition, the expression of BAG3 is closely related to immune cell infiltration and immune cell marker set. Conclusion BAG3 might be a potential therapeutic target and valuable prognostic biomarker of KIRC and is closely related to immune cell infiltration.
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spelling doaj.art-7ae5f5840bea45f7997fe040aaa27c872024-03-05T18:04:35ZengBMCEuropean Journal of Medical Research2047-783X2024-02-0129112010.1186/s40001-024-01687-wBAG3 as a novel prognostic biomarker in kidney renal clear cell carcinoma correlating with immune infiltratesBinghao Gong0Yuan Huang1Zhenting Wang2Bangbei Wan3Yaohui Zeng4Cai Lv5Department of Urology, Central South University Xiangya School of Medicine Affiliated Haikou HospitalDepartment of Neurology, Central South University Xiangya School of Medicine Affiliated Haikou HospitalDepartment of Urology, Central South University Xiangya School of Medicine Affiliated Haikou HospitalDepartment of Urology, Central South University Xiangya School of Medicine Affiliated Haikou HospitalDepartment of Urology, Central South University Xiangya School of Medicine Affiliated Haikou HospitalDepartment of Urology, Central South University Xiangya School of Medicine Affiliated Haikou HospitalAbstract Purpose BCL-2-associated athanogene 3 (BAG3) is an anti-apoptotic protein that plays an essential role in the onset and progression of multiple cancer types. However, the clinical significance of BAG3 in kidney renal clear cell carcinoma (KIRC) remains unclear. Methods Using Tumor IMmune Estimation Resource (TIMER), The Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) database, we explored the expression, prognostic value, and clinical correlations of BAG3 in KIRC. In addition, immunohistochemistry (IHC) of HKH cohort further validated the expression of BAG3 in KIRC and its impact on prognosis. Gene Set Cancer Analysis (GSCA) was utilized to scrutinize the prognostic value of BAG3 methylation. Gene Ontology (GO) term analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene set enrichment analysis (GSEA) were used to identify potential biological functions of BAG3 in KIRC. Single-sample gene set enrichment analysis (ssGSEA) was performed to confirm the correlation between BAG3 expression and immune cell infiltration. Results BAG3 mRNA expression and protein expression were significantly downregulated in KIRC tissues compared to normal kidney tissues, associated with adverse clinical–pathological factors and poor clinical prognosis. Multivariate Cox regression analysis indicated that low expression of BAG3 was an independent prognostic factor in KIRC patients. GSEA analysis showed that BAG3 is mainly involved in DNA methylation and the immune-related pathways in KIRC. In addition, the expression of BAG3 is closely related to immune cell infiltration and immune cell marker set. Conclusion BAG3 might be a potential therapeutic target and valuable prognostic biomarker of KIRC and is closely related to immune cell infiltration.https://doi.org/10.1186/s40001-024-01687-wBAG3PrognosisBiomarkerImmune infiltrateKidney clear cell carcinoma
spellingShingle Binghao Gong
Yuan Huang
Zhenting Wang
Bangbei Wan
Yaohui Zeng
Cai Lv
BAG3 as a novel prognostic biomarker in kidney renal clear cell carcinoma correlating with immune infiltrates
European Journal of Medical Research
BAG3
Prognosis
Biomarker
Immune infiltrate
Kidney clear cell carcinoma
title BAG3 as a novel prognostic biomarker in kidney renal clear cell carcinoma correlating with immune infiltrates
title_full BAG3 as a novel prognostic biomarker in kidney renal clear cell carcinoma correlating with immune infiltrates
title_fullStr BAG3 as a novel prognostic biomarker in kidney renal clear cell carcinoma correlating with immune infiltrates
title_full_unstemmed BAG3 as a novel prognostic biomarker in kidney renal clear cell carcinoma correlating with immune infiltrates
title_short BAG3 as a novel prognostic biomarker in kidney renal clear cell carcinoma correlating with immune infiltrates
title_sort bag3 as a novel prognostic biomarker in kidney renal clear cell carcinoma correlating with immune infiltrates
topic BAG3
Prognosis
Biomarker
Immune infiltrate
Kidney clear cell carcinoma
url https://doi.org/10.1186/s40001-024-01687-w
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