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BRCA1-Associated Protein Is a Potential Prognostic Biomarker and Is Correlated With Immune Infiltration in Liver Hepatocellular Carcinoma: A Pan-Cancer Analysis

BACKGROUND: BRCA1-associated protein (BRAP) is a critical gene that regulates inflammation-related signaling pathway and affects patients’ prognosis in esophageal squamous cell carcinoma (ESCC). However, its roles in different cancers remain largely unknown. METHODS: BRAP expression in human pan-can...

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Autores principales: Ju, Qiang, Li, Xin-mei, Zhang, Heng, Zhao, Yan-jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667264/
https://www.ncbi.nlm.nih.gov/pubmed/33240929
http://dx.doi.org/10.3389/fmolb.2020.573619
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author Ju, Qiang
Li, Xin-mei
Zhang, Heng
Zhao, Yan-jie
author_facet Ju, Qiang
Li, Xin-mei
Zhang, Heng
Zhao, Yan-jie
author_sort Ju, Qiang
collection PubMed
description BACKGROUND: BRCA1-associated protein (BRAP) is a critical gene that regulates inflammation-related signaling pathway and affects patients’ prognosis in esophageal squamous cell carcinoma (ESCC). However, its roles in different cancers remain largely unknown. METHODS: BRAP expression in human pan-cancer was analyzed via the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) database. Pearson correlation analysis was used to evaluate the association between BRAP expression with mismatch repair (MMR) gene mutation and DNA methyltransferase. We evaluated the influence of BRAP on clinical prognosis by univariate survival analysis. Moreover, the correlation between BRAP and tumor immune infiltration was analyzed via the Tumor Immune Evaluation Resource (TIMER) database. Pearson correlation analysis was used to investigate the correlation between BRAP expression and immune checkpoint genes expression. RESULTS: BRAP is abnormally overexpressed and significantly correlated with MMR gene mutation level and DNA methyltransferase expression in human pan-cancer. Univariate survival analysis showed that BRAP was significant with patients’ overall survival (OS) in six cancer types, disease-free interval (DFI) in three cancer types, and progression-free interval (PFI) in two cancer types. Remarkably, increased BRAP expression was strongly correlated with patients’ poor prognosis in liver hepatocellular carcinoma (LIHC), whether OS (P < 0.0001, hazard ratio (HR) = 1.1), DFI (P = 0.00099, HR = 1.06), or PFI (P = 0.00025, HR = 1.07). Moreover, a positive relationship was found between BRAP expression and immune infiltrating cells including B cell, CD4 + T cell, CD8 + T cell, dendritic cell, macrophage cell, and neutrophil cell in colon adenocarcinoma (COAD), kidney renal clear cell carcinoma (KIRC), and LIHC. Additionally, BRAP expression showed strong correlations with immune checkpoint genes in LIHC. CONCLUSION: BRAP expression is increased in human pan-cancer samples compared with normal tissues. Overexpression of BRAP is correlated with poor prognosis and immune infiltration in multiple cancers, especially in LIHC. These findings suggest that BRAP may be used as a potential molecular biomarker for determining prognosis and immune infiltration in LIHC.
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spelling pubmed-76672642020-11-24 BRCA1-Associated Protein Is a Potential Prognostic Biomarker and Is Correlated With Immune Infiltration in Liver Hepatocellular Carcinoma: A Pan-Cancer Analysis Ju, Qiang Li, Xin-mei Zhang, Heng Zhao, Yan-jie Front Mol Biosci Molecular Biosciences BACKGROUND: BRCA1-associated protein (BRAP) is a critical gene that regulates inflammation-related signaling pathway and affects patients’ prognosis in esophageal squamous cell carcinoma (ESCC). However, its roles in different cancers remain largely unknown. METHODS: BRAP expression in human pan-cancer was analyzed via the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) database. Pearson correlation analysis was used to evaluate the association between BRAP expression with mismatch repair (MMR) gene mutation and DNA methyltransferase. We evaluated the influence of BRAP on clinical prognosis by univariate survival analysis. Moreover, the correlation between BRAP and tumor immune infiltration was analyzed via the Tumor Immune Evaluation Resource (TIMER) database. Pearson correlation analysis was used to investigate the correlation between BRAP expression and immune checkpoint genes expression. RESULTS: BRAP is abnormally overexpressed and significantly correlated with MMR gene mutation level and DNA methyltransferase expression in human pan-cancer. Univariate survival analysis showed that BRAP was significant with patients’ overall survival (OS) in six cancer types, disease-free interval (DFI) in three cancer types, and progression-free interval (PFI) in two cancer types. Remarkably, increased BRAP expression was strongly correlated with patients’ poor prognosis in liver hepatocellular carcinoma (LIHC), whether OS (P < 0.0001, hazard ratio (HR) = 1.1), DFI (P = 0.00099, HR = 1.06), or PFI (P = 0.00025, HR = 1.07). Moreover, a positive relationship was found between BRAP expression and immune infiltrating cells including B cell, CD4 + T cell, CD8 + T cell, dendritic cell, macrophage cell, and neutrophil cell in colon adenocarcinoma (COAD), kidney renal clear cell carcinoma (KIRC), and LIHC. Additionally, BRAP expression showed strong correlations with immune checkpoint genes in LIHC. CONCLUSION: BRAP expression is increased in human pan-cancer samples compared with normal tissues. Overexpression of BRAP is correlated with poor prognosis and immune infiltration in multiple cancers, especially in LIHC. These findings suggest that BRAP may be used as a potential molecular biomarker for determining prognosis and immune infiltration in LIHC. Frontiers Media S.A. 2020-11-02 /pmc/articles/PMC7667264/ /pubmed/33240929 http://dx.doi.org/10.3389/fmolb.2020.573619 Text en Copyright © 2020 Ju, Li, Zhang and Zhao. http://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 Molecular Biosciences
Ju, Qiang
Li, Xin-mei
Zhang, Heng
Zhao, Yan-jie
BRCA1-Associated Protein Is a Potential Prognostic Biomarker and Is Correlated With Immune Infiltration in Liver Hepatocellular Carcinoma: A Pan-Cancer Analysis
title BRCA1-Associated Protein Is a Potential Prognostic Biomarker and Is Correlated With Immune Infiltration in Liver Hepatocellular Carcinoma: A Pan-Cancer Analysis
title_full BRCA1-Associated Protein Is a Potential Prognostic Biomarker and Is Correlated With Immune Infiltration in Liver Hepatocellular Carcinoma: A Pan-Cancer Analysis
title_fullStr BRCA1-Associated Protein Is a Potential Prognostic Biomarker and Is Correlated With Immune Infiltration in Liver Hepatocellular Carcinoma: A Pan-Cancer Analysis
title_full_unstemmed BRCA1-Associated Protein Is a Potential Prognostic Biomarker and Is Correlated With Immune Infiltration in Liver Hepatocellular Carcinoma: A Pan-Cancer Analysis
title_short BRCA1-Associated Protein Is a Potential Prognostic Biomarker and Is Correlated With Immune Infiltration in Liver Hepatocellular Carcinoma: A Pan-Cancer Analysis
title_sort brca1-associated protein is a potential prognostic biomarker and is correlated with immune infiltration in liver hepatocellular carcinoma: a pan-cancer analysis
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667264/
https://www.ncbi.nlm.nih.gov/pubmed/33240929
http://dx.doi.org/10.3389/fmolb.2020.573619
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