Overexpression of DBT suppresses the aggressiveness of renal clear cell carcinoma and correlates with immune infiltration

Abstract

Conventional therapy for kidney renal clear cell carcinoma (KIRC) is unpromising. The tumor microenvironment (TME) is intimately linked to the invasiveness of a variety of tumor forms, including KIRC. The purpose of this research is to establish the prognostic and immune-related significance of dihydrolipoamide branched chain transacylase E2 (DBT) in individuals with KIRC. In this investigation, we discovered that DBT expression was down-regulated in a range of human malignancies, and low DBT expression in KIRC was linked to higher-level clinicopathological characteristics as well as a poor prognosis for KIRC patients. Based on the findings of univariate and multivariate Cox regression analyses, DBT might be employed as an independent prognostic factor in KIRC patients. Furthermore, we developed a nomogram to better investigate DBT’s predictive usefulness. To confirm DBT expression, we examined KIRC cell lines using RT-qPCR and Western blotting. We also examined the role of DBT in KIRC using colony formation, CCK-8, EdU, transwell, and wound healing assays. We discovered that plasmid-mediated overexpression of DBT in KIRC cells slowed cell proliferation and decreased migration and invasion. Multiple enrichment analyses revealed that DBT may be involved in processes and pathways related to immunotherapy and drug metabolism. We computed the immune infiltration score and discovered that the immunological score and the ESTIMATE score were both greater in the DBT low expression group. According to the CIBERSORT algorithm, DBT seems to promote anti-cancer immune responses in KIRC by activating M1 macrophages, mast cells, and dendritic cells while inhibiting regulatory T cells. Finally, in KIRC, DBT expression was found to be highly linked to immunological checkpoints, targeted medicines, and immunotherapeutic agents. Our findings suggest that DBT is a distinct predictive biomarker for KIRC patients, playing a significant role in the TME of KIRC and serving as a reference for the selection of targeted treatment and immunotherapy.

Comprehensive molecular analyses of cuproptosis-related genes with regard to prognosis, immune landscape, and response to immune checkpoint blockers in lung adenocarcinoma

“…DBT has been characterized as a tumor suppressor that inhibits tumor progression and corrects lipid metabolism disorders through the DBT/ANXA2/ YAP axis-regulated Hippo signaling pathway in clear cell renal cell carcinoma (Miao et al 2023). DBT expression has also been recognized as an independent prognostic factor in kidney renal clear cell carcinoma, highly correlated with immunological checkpoints and targeted medications (Zhang et al 2023). In this study, a strong positive correlation was observed between DLAT and DBT expression levels in patients with LUAD.…”

Underlying mechanisms of novel cuproptosis-related dihydrolipoamide branched-chain transacylase E2 (DBT) signature in sunitinib-resistant clear-cell renal cell carcinoma

“…The CIBERSORT algorithm analysis implies that DBT may enhance anti-cancer immune responses in KIRC by activating M1 macrophages, mast cells, and dendritic cells, and concurrently reducing regulatory T cell activity. Lastly, DBT expression in KIRC has been found to have a strong association with immune checkpoints and the efficacy of targeted and immunotherapy drugs [ 52 ].…”