Department of Urology, Central South University Xiangya School of Medicine Affiliated Haikou Hospital, Haikou, China.
Department of Neurology, Central South University Xiangya School of Medicine Affiliated Haikou Hospital, Haikou, China.
Eur J Med Res. 2024 Feb 1;29(1):93. doi: 10.1186/s40001-024-01687-w.
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.
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.
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.
BAG3 might be a potential therapeutic target and valuable prognostic biomarker of KIRC and is closely related to immune cell infiltration.
B 细胞淋巴瘤-2 相关抗凋亡基因 3（BAG3）是一种抗凋亡蛋白，在多种癌症类型的发生和发展中起着至关重要的作用。然而，BAG3 在肾透明细胞癌（KIRC）中的临床意义尚不清楚。
利用肿瘤免疫估计资源（TIMER）、癌症基因组图谱（TCGA）和基因表达综合数据库（GEO），我们探讨了 BAG3 在 KIRC 中的表达、预后价值和临床相关性。此外，HKH 队列的免疫组织化学（IHC）进一步验证了 BAG3 在 KIRC 中的表达及其对预后的影响。基因集癌症分析（GSCA）用于研究 BAG3 甲基化的预后价值。基因本体论（GO）术语分析、京都基因与基因组百科全书（KEGG）和基因集富集分析（GSEA）用于鉴定 BAG3 在 KIRC 中的潜在生物学功能。单样本基因集富集分析（ssGSEA）用于确认 BAG3 表达与免疫细胞浸润的相关性。
与正常肾组织相比，KIRC 组织中 BAG3 mRNA 表达和蛋白表达明显下调，与不良临床病理因素和不良临床预后相关。多因素 Cox 回归分析表明，BAG3 低表达是 KIRC 患者的独立预后因素。GSEA 分析表明，BAG3 主要参与 KIRC 中的 DNA 甲基化和免疫相关途径。此外，BAG3 的表达与免疫细胞浸润和免疫细胞标志物集密切相关。
BAG3 可能是 KIRC 的潜在治疗靶点和有价值的预后生物标志物，与免疫细胞浸润密切相关。
