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Vemurafenib inhibits immune escape biomarker BCL2A1 by targeting PI3K/AKT signaling pathway to suppress breast cancer

OBJECTIVES: To investigate the role of immune escape encoding genes on the prognosis of BC, and to predict the novel targeting agents. METHODS: Human immune genes and immune escape encoding genes were obtained from the IMMPORT database and the previous study. Sample information and clinical data on...

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Autores principales: Dai, Yalan, Yang, Liqiong, Sakandar, Abass, Zhang, Duoli, Du, Fukuan, Zhang, Xinyi, Zou, Linglin, Zhao, Yueshui, Wang, Jigang, Zhang, Zhenhua, Wu, Xu, Li, Mingxing, Ling, Xiao, Yu, Lei, Dong, Lishu, Shen, Jing, Xiao, Zhangang, Wen, Qinglian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9745811/
https://www.ncbi.nlm.nih.gov/pubmed/36524001
http://dx.doi.org/10.3389/fonc.2022.906197
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author Dai, Yalan
Yang, Liqiong
Sakandar, Abass
Zhang, Duoli
Du, Fukuan
Zhang, Xinyi
Zou, Linglin
Zhao, Yueshui
Wang, Jigang
Zhang, Zhenhua
Wu, Xu
Li, Mingxing
Ling, Xiao
Yu, Lei
Dong, Lishu
Shen, Jing
Xiao, Zhangang
Wen, Qinglian
author_facet Dai, Yalan
Yang, Liqiong
Sakandar, Abass
Zhang, Duoli
Du, Fukuan
Zhang, Xinyi
Zou, Linglin
Zhao, Yueshui
Wang, Jigang
Zhang, Zhenhua
Wu, Xu
Li, Mingxing
Ling, Xiao
Yu, Lei
Dong, Lishu
Shen, Jing
Xiao, Zhangang
Wen, Qinglian
author_sort Dai, Yalan
collection PubMed
description OBJECTIVES: To investigate the role of immune escape encoding genes on the prognosis of BC, and to predict the novel targeting agents. METHODS: Human immune genes and immune escape encoding genes were obtained from the IMMPORT database and the previous study. Sample information and clinical data on BC were obtained from the TCGA and GTEX databases. Obtaining differentially expressed protein data from cBioportal database. To construct a risk score model by lasso analysis, and nomogram was used to predict score core. GSCA, TIMER and CELLMINER databases were used for immune and drug susceptibility correlation analyses. Cell experiments were verified by MTT, Western blotting, and RT-qPCR. RESULTS: We found prognostic models consisting of eleven immune escape related protein-coding genes with ROC curves that performed well in the ontology data (AUC for TCGA is 0.672) and the external data (AUC for GSE20685 is 0.663 and for GES42568 is 0.706). Five core prognostic models are related to survival (EIF4EBP1, BCL2A1, NDRG1, ERRFI1 and BRD4) were summarized, and a nomogram was constructed to validate a C-index of 0.695, which was superior to other prognostic models. Relevant drugs targeting core genes were identified based on drug sensitivity analysis, and found that Vemurafenib downregulates the PI3K-AKT pathway and BCL2A1 protein in BC, as confirmed by external data and cellular assays. CONCLUSIONS: Briefly, our work establishes and validates an 11-immune escape risk model, and five core prognostic factors that are mined deeply from this model, and elucidates in detail that Vemurafenib suppresses breast cancer by targeting the PI3K/AKT signaling pathway to inhibit the immune escape biomarker BCL2A1, confirms the validity of the prognostic model, and provides corresponding targeted agents to guide individualized treatment of BC patients.
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spelling pubmed-97458112022-12-14 Vemurafenib inhibits immune escape biomarker BCL2A1 by targeting PI3K/AKT signaling pathway to suppress breast cancer Dai, Yalan Yang, Liqiong Sakandar, Abass Zhang, Duoli Du, Fukuan Zhang, Xinyi Zou, Linglin Zhao, Yueshui Wang, Jigang Zhang, Zhenhua Wu, Xu Li, Mingxing Ling, Xiao Yu, Lei Dong, Lishu Shen, Jing Xiao, Zhangang Wen, Qinglian Front Oncol Oncology OBJECTIVES: To investigate the role of immune escape encoding genes on the prognosis of BC, and to predict the novel targeting agents. METHODS: Human immune genes and immune escape encoding genes were obtained from the IMMPORT database and the previous study. Sample information and clinical data on BC were obtained from the TCGA and GTEX databases. Obtaining differentially expressed protein data from cBioportal database. To construct a risk score model by lasso analysis, and nomogram was used to predict score core. GSCA, TIMER and CELLMINER databases were used for immune and drug susceptibility correlation analyses. Cell experiments were verified by MTT, Western blotting, and RT-qPCR. RESULTS: We found prognostic models consisting of eleven immune escape related protein-coding genes with ROC curves that performed well in the ontology data (AUC for TCGA is 0.672) and the external data (AUC for GSE20685 is 0.663 and for GES42568 is 0.706). Five core prognostic models are related to survival (EIF4EBP1, BCL2A1, NDRG1, ERRFI1 and BRD4) were summarized, and a nomogram was constructed to validate a C-index of 0.695, which was superior to other prognostic models. Relevant drugs targeting core genes were identified based on drug sensitivity analysis, and found that Vemurafenib downregulates the PI3K-AKT pathway and BCL2A1 protein in BC, as confirmed by external data and cellular assays. CONCLUSIONS: Briefly, our work establishes and validates an 11-immune escape risk model, and five core prognostic factors that are mined deeply from this model, and elucidates in detail that Vemurafenib suppresses breast cancer by targeting the PI3K/AKT signaling pathway to inhibit the immune escape biomarker BCL2A1, confirms the validity of the prognostic model, and provides corresponding targeted agents to guide individualized treatment of BC patients. Frontiers Media S.A. 2022-11-29 /pmc/articles/PMC9745811/ /pubmed/36524001 http://dx.doi.org/10.3389/fonc.2022.906197 Text en Copyright © 2022 Dai, Yang, Sakandar, Zhang, Du, Zhang, Zou, Zhao, Wang, Zhang, Wu, Li, Ling, Yu, Dong, Shen, Xiao and Wen 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 Oncology
Dai, Yalan
Yang, Liqiong
Sakandar, Abass
Zhang, Duoli
Du, Fukuan
Zhang, Xinyi
Zou, Linglin
Zhao, Yueshui
Wang, Jigang
Zhang, Zhenhua
Wu, Xu
Li, Mingxing
Ling, Xiao
Yu, Lei
Dong, Lishu
Shen, Jing
Xiao, Zhangang
Wen, Qinglian
Vemurafenib inhibits immune escape biomarker BCL2A1 by targeting PI3K/AKT signaling pathway to suppress breast cancer
title Vemurafenib inhibits immune escape biomarker BCL2A1 by targeting PI3K/AKT signaling pathway to suppress breast cancer
title_full Vemurafenib inhibits immune escape biomarker BCL2A1 by targeting PI3K/AKT signaling pathway to suppress breast cancer
title_fullStr Vemurafenib inhibits immune escape biomarker BCL2A1 by targeting PI3K/AKT signaling pathway to suppress breast cancer
title_full_unstemmed Vemurafenib inhibits immune escape biomarker BCL2A1 by targeting PI3K/AKT signaling pathway to suppress breast cancer
title_short Vemurafenib inhibits immune escape biomarker BCL2A1 by targeting PI3K/AKT signaling pathway to suppress breast cancer
title_sort vemurafenib inhibits immune escape biomarker bcl2a1 by targeting pi3k/akt signaling pathway to suppress breast cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9745811/
https://www.ncbi.nlm.nih.gov/pubmed/36524001
http://dx.doi.org/10.3389/fonc.2022.906197
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