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.

Protein Quality Control in Glioblastoma: A Review of the Current Literature with New Perspectives on Therapeutic Targets

“…The BAG family acts athánatos—the Greek term “against death” for which these proteins are named [ 95 ]. Cancer cells inherently share this behavior, and multiple cancer types have been linked to the Bag proteins ( Table 2 ) [ 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 ]. Given the myriad ways in which Bag1–6 and their cochaperones have been observed in oncology, the therapeutic potential of PQC manipulation at the level of the directional proteins is not limited to glioblastoma.…”

“…While many pharmaceuticals target the downstream pathways of UPS and ALP, the anthogenes are predominantly explored as prognostic indicators rather than as interventions [ 99 , 101 , 102 , 104 ]. Further investigation is warranted to enhance pre-existing therapies at the level of anti-apoptotic Bag3, which promotes cell survival early in the PQC decision-making process.…”