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

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.

Keywords: BAG1; Fatty acid metabolism; KIRC; Oxidative phosphorylation; Prognosis.

Fig. 1

Downregulation of BAG1 expression in KIRC and survival analysis. a BAG1 mRNA expression in TCGA KIRC tissues and adjacent normal tissues. b BAG1 expression in GEO Dataset. c-d BAG1 correlated with OS and DFS in TCGA KIRC patients (P < 0.001)

Fig. 2

Association between BAG1 expression and clinicopathologic variables of patients with KIRC in TCGA. a-i BAG1 mRNA expression as a continuous variable significantly correlated with clinical stage, tumor size, lymph node metastasis, distant metastasis, grade, gender, serum hemoglobin level and cancer status

Fig. 3

Enrichment plots from gene set enrichment analysis (GSEA). GSEA results showing some pathways such as fatty acid metabolism and oxidative phosphorylation are differentially enriched in BAG1-related KIRC. The enrichment score (ES, green line) means the degree to which the gene set is overrepresented at the top or bottom of the ranked list of genes