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Comprehensive analysis and establishment of a prediction model of alternative splicing events reveal the prognostic predictor and immune microenvironment signatures in triple negative breast cancer

BACKGROUND: Triple-negative breast cancer (TNBC) is widely concerning because of high malignancy and poor prognosis. There is increasing evidence that alternative splicing (AS) plays an important role in the development of cancer and the formation of the tumour microenvironment. However, comprehensi...

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Autores principales: Yu, Shanshan, Hu, Chuan, Liu, Lixiao, Cai, Luya, Du, Xuedan, Yu, Qiongjie, Lin, Fan, Zhao, Jinduo, Zhao, Ye, Zhang, Cheng, Liu, Xuan, Li, Wenfeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388537/
https://www.ncbi.nlm.nih.gov/pubmed/32723333
http://dx.doi.org/10.1186/s12967-020-02454-1
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author Yu, Shanshan
Hu, Chuan
Liu, Lixiao
Cai, Luya
Du, Xuedan
Yu, Qiongjie
Lin, Fan
Zhao, Jinduo
Zhao, Ye
Zhang, Cheng
Liu, Xuan
Li, Wenfeng
author_facet Yu, Shanshan
Hu, Chuan
Liu, Lixiao
Cai, Luya
Du, Xuedan
Yu, Qiongjie
Lin, Fan
Zhao, Jinduo
Zhao, Ye
Zhang, Cheng
Liu, Xuan
Li, Wenfeng
author_sort Yu, Shanshan
collection PubMed
description BACKGROUND: Triple-negative breast cancer (TNBC) is widely concerning because of high malignancy and poor prognosis. There is increasing evidence that alternative splicing (AS) plays an important role in the development of cancer and the formation of the tumour microenvironment. However, comprehensive analysis of AS signalling in TNBC is still lacking and urgently needed. METHODS: Transcriptome and clinical data of 169 TNBC tissues and 15 normal tissues were obtained and integrated from the cancer genome atlas (TCGA), and an overview of AS events was downloaded from the SpliceSeq database. Then, differential comparative analysis was performed to obtain cancer-associated AS events (CAAS). Metascape was used to perform parent gene enrichment analysis based on CAAS. Unsupervised cluster analysis was performed to analyse the characteristics of immune infiltration in the microenvironment. A splicing network was established based on the correlation between CAAS events and splicing factors (SFs). We then constructed prediction models and assessed the accuracy of these models by receiver operating characteristic (ROC) curve and Kaplan–Meier survival analyses. Furthermore, a nomogram was adopted to predict the individualized survival rate of TNBC patients. RESULTS: We identified 1194 cancer-associated AS events (CAAS) and evaluated the enrichment of 981 parent genes. The top 20 parent genes with significant differences were mostly related to cell adhesion, cell component connection and other pathways. Furthermore, immune-related pathways were also enriched. Unsupervised clustering analysis revealed the heterogeneity of the immune microenvironment in TNBC. The splicing network also suggested an obvious correlation between SFs expression and CAAS events in TNBC patients. Univariate and multivariate Cox regression analyses showed that the survival-related AS events were detected, including some significant participants in the carcinogenic process. A nomogram incorporating risk, AJCC and radiotherapy showed good calibration and moderate discrimination. CONCLUSION: Our study revealed AS events related to tumorigenesis and the immune microenvironment, elaborated the potential correlation between SFs and CAAS, established a prognostic model based on survival-related AS events, and created a nomogram to better predict the individual survival rate of TNBC patients, which improved our understanding of the relationship between AS events and TNBC.
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spelling pubmed-73885372020-07-31 Comprehensive analysis and establishment of a prediction model of alternative splicing events reveal the prognostic predictor and immune microenvironment signatures in triple negative breast cancer Yu, Shanshan Hu, Chuan Liu, Lixiao Cai, Luya Du, Xuedan Yu, Qiongjie Lin, Fan Zhao, Jinduo Zhao, Ye Zhang, Cheng Liu, Xuan Li, Wenfeng J Transl Med Research BACKGROUND: Triple-negative breast cancer (TNBC) is widely concerning because of high malignancy and poor prognosis. There is increasing evidence that alternative splicing (AS) plays an important role in the development of cancer and the formation of the tumour microenvironment. However, comprehensive analysis of AS signalling in TNBC is still lacking and urgently needed. METHODS: Transcriptome and clinical data of 169 TNBC tissues and 15 normal tissues were obtained and integrated from the cancer genome atlas (TCGA), and an overview of AS events was downloaded from the SpliceSeq database. Then, differential comparative analysis was performed to obtain cancer-associated AS events (CAAS). Metascape was used to perform parent gene enrichment analysis based on CAAS. Unsupervised cluster analysis was performed to analyse the characteristics of immune infiltration in the microenvironment. A splicing network was established based on the correlation between CAAS events and splicing factors (SFs). We then constructed prediction models and assessed the accuracy of these models by receiver operating characteristic (ROC) curve and Kaplan–Meier survival analyses. Furthermore, a nomogram was adopted to predict the individualized survival rate of TNBC patients. RESULTS: We identified 1194 cancer-associated AS events (CAAS) and evaluated the enrichment of 981 parent genes. The top 20 parent genes with significant differences were mostly related to cell adhesion, cell component connection and other pathways. Furthermore, immune-related pathways were also enriched. Unsupervised clustering analysis revealed the heterogeneity of the immune microenvironment in TNBC. The splicing network also suggested an obvious correlation between SFs expression and CAAS events in TNBC patients. Univariate and multivariate Cox regression analyses showed that the survival-related AS events were detected, including some significant participants in the carcinogenic process. A nomogram incorporating risk, AJCC and radiotherapy showed good calibration and moderate discrimination. CONCLUSION: Our study revealed AS events related to tumorigenesis and the immune microenvironment, elaborated the potential correlation between SFs and CAAS, established a prognostic model based on survival-related AS events, and created a nomogram to better predict the individual survival rate of TNBC patients, which improved our understanding of the relationship between AS events and TNBC. BioMed Central 2020-07-28 /pmc/articles/PMC7388537/ /pubmed/32723333 http://dx.doi.org/10.1186/s12967-020-02454-1 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Yu, Shanshan
Hu, Chuan
Liu, Lixiao
Cai, Luya
Du, Xuedan
Yu, Qiongjie
Lin, Fan
Zhao, Jinduo
Zhao, Ye
Zhang, Cheng
Liu, Xuan
Li, Wenfeng
Comprehensive analysis and establishment of a prediction model of alternative splicing events reveal the prognostic predictor and immune microenvironment signatures in triple negative breast cancer
title Comprehensive analysis and establishment of a prediction model of alternative splicing events reveal the prognostic predictor and immune microenvironment signatures in triple negative breast cancer
title_full Comprehensive analysis and establishment of a prediction model of alternative splicing events reveal the prognostic predictor and immune microenvironment signatures in triple negative breast cancer
title_fullStr Comprehensive analysis and establishment of a prediction model of alternative splicing events reveal the prognostic predictor and immune microenvironment signatures in triple negative breast cancer
title_full_unstemmed Comprehensive analysis and establishment of a prediction model of alternative splicing events reveal the prognostic predictor and immune microenvironment signatures in triple negative breast cancer
title_short Comprehensive analysis and establishment of a prediction model of alternative splicing events reveal the prognostic predictor and immune microenvironment signatures in triple negative breast cancer
title_sort comprehensive analysis and establishment of a prediction model of alternative splicing events reveal the prognostic predictor and immune microenvironment signatures in triple negative breast cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388537/
https://www.ncbi.nlm.nih.gov/pubmed/32723333
http://dx.doi.org/10.1186/s12967-020-02454-1
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