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

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 dihy...

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Autores principales: Zhang, Chiyu, Huang, Gaomin, Yang, Jiale, Jiang, Yi, Huang, Ruizhen, Ye, Zhenfeng, Huang, Yawei, Hu, Honglin, Xi, Xiaoqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10293648/
https://www.ncbi.nlm.nih.gov/pubmed/37383233
http://dx.doi.org/10.3389/fimmu.2023.1197011
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author Zhang, Chiyu
Huang, Gaomin
Yang, Jiale
Jiang, Yi
Huang, Ruizhen
Ye, Zhenfeng
Huang, Yawei
Hu, Honglin
Xi, Xiaoqing
author_facet Zhang, Chiyu
Huang, Gaomin
Yang, Jiale
Jiang, Yi
Huang, Ruizhen
Ye, Zhenfeng
Huang, Yawei
Hu, Honglin
Xi, Xiaoqing
author_sort Zhang, Chiyu
collection PubMed
description 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.
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spelling pubmed-102936482023-06-28 Overexpression of DBT suppresses the aggressiveness of renal clear cell carcinoma and correlates with immune infiltration Zhang, Chiyu Huang, Gaomin Yang, Jiale Jiang, Yi Huang, Ruizhen Ye, Zhenfeng Huang, Yawei Hu, Honglin Xi, Xiaoqing Front Immunol Immunology 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. Frontiers Media S.A. 2023-06-13 /pmc/articles/PMC10293648/ /pubmed/37383233 http://dx.doi.org/10.3389/fimmu.2023.1197011 Text en Copyright © 2023 Zhang, Huang, Yang, Jiang, Huang, Ye, Huang, Hu and Xi https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Zhang, Chiyu
Huang, Gaomin
Yang, Jiale
Jiang, Yi
Huang, Ruizhen
Ye, Zhenfeng
Huang, Yawei
Hu, Honglin
Xi, Xiaoqing
Overexpression of DBT suppresses the aggressiveness of renal clear cell carcinoma and correlates with immune infiltration
title Overexpression of DBT suppresses the aggressiveness of renal clear cell carcinoma and correlates with immune infiltration
title_full Overexpression of DBT suppresses the aggressiveness of renal clear cell carcinoma and correlates with immune infiltration
title_fullStr Overexpression of DBT suppresses the aggressiveness of renal clear cell carcinoma and correlates with immune infiltration
title_full_unstemmed Overexpression of DBT suppresses the aggressiveness of renal clear cell carcinoma and correlates with immune infiltration
title_short Overexpression of DBT suppresses the aggressiveness of renal clear cell carcinoma and correlates with immune infiltration
title_sort overexpression of dbt suppresses the aggressiveness of renal clear cell carcinoma and correlates with immune infiltration
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10293648/
https://www.ncbi.nlm.nih.gov/pubmed/37383233
http://dx.doi.org/10.3389/fimmu.2023.1197011
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