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

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机构: [1]Department of Oncology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China. [2]Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China. [3]Cell Therapy & Cell Drugs, Luzhou Key Laboratory, Luzhou, China. [4]South Sichuan Institute of Translational Medicine, Southwest Medical University, Luzhou, China. [5]School of Data Science, The Chinese University of Hong Kong, Shenzhen, China. [6]Shenzhen Municipal People's Hospital, Shenzhen, China. [7]Department of Obstetrics, Luzhou Maternal & Child Health Hospital (Luzhou Second People's Hospital), Luzhou, Sichuan, China.
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关键词: Immune escape breast cancer prognostic model bioinformatics biomarker BCL2A1 vemurafenib PI3K/Akt signaling pathway

摘要:
To investigate the role of immune escape encoding genes on the prognosis of BC, and to predict the novel targeting agents.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.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.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.Copyright © 2022 Dai, Yang, Sakandar, Zhang, Du, Zhang, Zou, Zhao, Wang, Zhang, Wu, Li, Ling, Yu, Dong, Shen, Xiao and Wen.

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出版当年[2022]版:
大类 | 3 区 医学
小类 | 3 区 肿瘤学
最新[2023]版:
大类 | 3 区 医学
小类 | 3 区 肿瘤学
第一作者:
第一作者机构: [1]Department of Oncology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China.
通讯作者:
通讯机构: [2]Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China. [3]Cell Therapy & Cell Drugs, Luzhou Key Laboratory, Luzhou, China. [4]South Sichuan Institute of Translational Medicine, Southwest Medical University, Luzhou, China.
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