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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Format: | Article |
Language: | English |
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BMC
2024-02-01
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Series: | European Journal of Medical Research |
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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. |
first_indexed | 2024-03-07T15:13:07Z |
format | Article |
id | doaj.art-7ae5f5840bea45f7997fe040aaa27c87 |
institution | Directory Open Access Journal |
issn | 2047-783X |
language | English |
last_indexed | 2024-03-07T15:13:07Z |
publishDate | 2024-02-01 |
publisher | BMC |
record_format | Article |
series | European Journal of Medical Research |
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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