NFAT as a Biomarker and Therapeutic Target in Non–Small Cell Lung Cancer–Related Brain Metastasis

BackgroundBrain metastases (BMs) are associated with poor prognosis and significant mortality, and approximately 25% of patients with non–small cell lung cancer (NSCLC) develop BMs. The present study was aimed to understand the relationships between BM and NSCLC and reveal potential biomarkers and t...

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Autores principales: Lu Peng, Yihao Tao, Rui Wu, Jing Su, Maoyuan Sun, Yuan Cheng, Zongyi Xie, Jinning Mao, Xiaohui Zhan, Guodong Liu
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Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/2308467c2aae4f49ae1a3c94ad377e56
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spelling oai:doaj.org-article:2308467c2aae4f49ae1a3c94ad377e562021-12-01T17:07:43ZNFAT as a Biomarker and Therapeutic Target in Non–Small Cell Lung Cancer–Related Brain Metastasis2234-943X10.3389/fonc.2021.781150https://doaj.org/article/2308467c2aae4f49ae1a3c94ad377e562021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.781150/fullhttps://doaj.org/toc/2234-943XBackgroundBrain metastases (BMs) are associated with poor prognosis and significant mortality, and approximately 25% of patients with non–small cell lung cancer (NSCLC) develop BMs. The present study was aimed to understand the relationships between BM and NSCLC and reveal potential biomarkers and therapeutic targets in NSCLC-related BM.MethodsThe differentially expressed genes (DEGs) expressed during NSCLC and BM development were predicted by bioinformatics analysis, and the expression of the upstream transcription factor nuclear factor of activated T cells (NFAT) was confirmed as a differential gene expressed in both NSCLC and BM. In addition, the expression of proteins encoded by these DEGs was verified by immunohistochemical experiments examining normal lung tissue, lung cancer tissue, and brain metastasis tissue from 30 patients with NSCLC related BM.ResultsThe co-DEGs interleukin (IL)-11, cadherin 5 (CDH5) and C-C motif chemokine 2 (CCL2) link NSCLC and BM in the Gene Expression Omnibus (GEO) database, and NFAT may target the expression of these co-DEGs. In the GEO database, NFATc1 and NFATc3 were significantly downregulated in NSCLC tissues (P <.05), whereas NFATc1, NFATc2, NFATc3, and NFATc4 were significantly downregulated in BMs (P <.05). Consistent findings were observed in the immunohistochemical analysis.ConclusionNFATc1 and NFATc3 may play important roles in the occurrence of NSCLC and BM by regulating IL-11, CDH5, and CCL2.Lu PengYihao TaoRui WuJing SuMaoyuan SunYuan ChengZongyi XieJinning MaoXiaohui ZhanGuodong LiuFrontiers Media S.A.articlenon–small cell lung cancerbrain metastasisbiomarkerbioinformaticsimmunohistochemistryNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution DOAJ
collection DOAJ
language EN
topic non–small cell lung cancer
brain metastasis
biomarker
bioinformatics
immunohistochemistry
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle non–small cell lung cancer
brain metastasis
biomarker
bioinformatics
immunohistochemistry
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Lu Peng
Yihao Tao
Rui Wu
Jing Su
Maoyuan Sun
Yuan Cheng
Zongyi Xie
Jinning Mao
Xiaohui Zhan
Guodong Liu
NFAT as a Biomarker and Therapeutic Target in Non–Small Cell Lung Cancer–Related Brain Metastasis
description BackgroundBrain metastases (BMs) are associated with poor prognosis and significant mortality, and approximately 25% of patients with non–small cell lung cancer (NSCLC) develop BMs. The present study was aimed to understand the relationships between BM and NSCLC and reveal potential biomarkers and therapeutic targets in NSCLC-related BM.MethodsThe differentially expressed genes (DEGs) expressed during NSCLC and BM development were predicted by bioinformatics analysis, and the expression of the upstream transcription factor nuclear factor of activated T cells (NFAT) was confirmed as a differential gene expressed in both NSCLC and BM. In addition, the expression of proteins encoded by these DEGs was verified by immunohistochemical experiments examining normal lung tissue, lung cancer tissue, and brain metastasis tissue from 30 patients with NSCLC related BM.ResultsThe co-DEGs interleukin (IL)-11, cadherin 5 (CDH5) and C-C motif chemokine 2 (CCL2) link NSCLC and BM in the Gene Expression Omnibus (GEO) database, and NFAT may target the expression of these co-DEGs. In the GEO database, NFATc1 and NFATc3 were significantly downregulated in NSCLC tissues (P <.05), whereas NFATc1, NFATc2, NFATc3, and NFATc4 were significantly downregulated in BMs (P <.05). Consistent findings were observed in the immunohistochemical analysis.ConclusionNFATc1 and NFATc3 may play important roles in the occurrence of NSCLC and BM by regulating IL-11, CDH5, and CCL2.
format article
author Lu Peng
Yihao Tao
Rui Wu
Jing Su
Maoyuan Sun
Yuan Cheng
Zongyi Xie
Jinning Mao
Xiaohui Zhan
Guodong Liu
author_facet Lu Peng
Yihao Tao
Rui Wu
Jing Su
Maoyuan Sun
Yuan Cheng
Zongyi Xie
Jinning Mao
Xiaohui Zhan
Guodong Liu
author_sort Lu Peng
title NFAT as a Biomarker and Therapeutic Target in Non–Small Cell Lung Cancer–Related Brain Metastasis
title_short NFAT as a Biomarker and Therapeutic Target in Non–Small Cell Lung Cancer–Related Brain Metastasis
title_full NFAT as a Biomarker and Therapeutic Target in Non–Small Cell Lung Cancer–Related Brain Metastasis
title_fullStr NFAT as a Biomarker and Therapeutic Target in Non–Small Cell Lung Cancer–Related Brain Metastasis
title_full_unstemmed NFAT as a Biomarker and Therapeutic Target in Non–Small Cell Lung Cancer–Related Brain Metastasis
title_sort nfat as a biomarker and therapeutic target in non–small cell lung cancer–related brain metastasis
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/2308467c2aae4f49ae1a3c94ad377e56
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