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The pattern of alternative splicing in lung adenocarcinoma shows novel events correlated with tumorigenesis and immune microenvironment

Lung adenocarcinoma (LUAD) is the leading cause of cancer deaths worldwide due to the lack of early diagnostic markers and specific drugs. Previous studies have shown the association of LUAD growth with aberrant alternative splicing (AS). Herein, clinical data of 535 tumor tissues and 59 normal tiss...

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Autores principales: Wang, Gongjun, Qi, Weiwei, Shen, Liwei, Wang, Shasha, Xiao, Ruoxi, Li, Wenqian, Zhang, Yuqi, Bian, Xiaoqian, Sun, Libin, Qiu, Wensheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8647402/
https://www.ncbi.nlm.nih.gov/pubmed/34872548
http://dx.doi.org/10.1186/s12890-021-01776-0
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author Wang, Gongjun
Qi, Weiwei
Shen, Liwei
Wang, Shasha
Xiao, Ruoxi
Li, Wenqian
Zhang, Yuqi
Bian, Xiaoqian
Sun, Libin
Qiu, Wensheng
author_facet Wang, Gongjun
Qi, Weiwei
Shen, Liwei
Wang, Shasha
Xiao, Ruoxi
Li, Wenqian
Zhang, Yuqi
Bian, Xiaoqian
Sun, Libin
Qiu, Wensheng
author_sort Wang, Gongjun
collection PubMed
description Lung adenocarcinoma (LUAD) is the leading cause of cancer deaths worldwide due to the lack of early diagnostic markers and specific drugs. Previous studies have shown the association of LUAD growth with aberrant alternative splicing (AS). Herein, clinical data of 535 tumor tissues and 59 normal tissues were extracted from The Cancer Genome Atlas (TCGA) database. Each sample was analyzed using the ESTIMATE algorithm; a comparison between higher and lower score groups (stromal or immune) was made to determine the overall- and progression-free survival-related differentially expressed AS (DEAS) events. We then performed unsupervised clustering of these DEASs, followed by determining their relationship with survival rate, immune cells, and the tumor microenvironment (TME). Next, two prognostic signatures were developed using bioinformatics tools to explore the prognosis of cases with LUAD. Five OS- and six PFS-associated DEAS events were implemented to establish a prognostic risk score model. When compared to the high-risk group (HRG), the PFS and OS of the low-risk group (LRG) were found to be considerable. Additionally, a better prognosis was found considerably associated with the ESTIMATE score of the patients as well as immune cells infiltration. Our analysis of AS events in LUAD not only helps to clarify the tumorigenesis mechanism of AS but also provides ideas for revealing potential prognostic biomarkers and therapeutic targets. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12890-021-01776-0.
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spelling pubmed-86474022021-12-07 The pattern of alternative splicing in lung adenocarcinoma shows novel events correlated with tumorigenesis and immune microenvironment Wang, Gongjun Qi, Weiwei Shen, Liwei Wang, Shasha Xiao, Ruoxi Li, Wenqian Zhang, Yuqi Bian, Xiaoqian Sun, Libin Qiu, Wensheng BMC Pulm Med Research Lung adenocarcinoma (LUAD) is the leading cause of cancer deaths worldwide due to the lack of early diagnostic markers and specific drugs. Previous studies have shown the association of LUAD growth with aberrant alternative splicing (AS). Herein, clinical data of 535 tumor tissues and 59 normal tissues were extracted from The Cancer Genome Atlas (TCGA) database. Each sample was analyzed using the ESTIMATE algorithm; a comparison between higher and lower score groups (stromal or immune) was made to determine the overall- and progression-free survival-related differentially expressed AS (DEAS) events. We then performed unsupervised clustering of these DEASs, followed by determining their relationship with survival rate, immune cells, and the tumor microenvironment (TME). Next, two prognostic signatures were developed using bioinformatics tools to explore the prognosis of cases with LUAD. Five OS- and six PFS-associated DEAS events were implemented to establish a prognostic risk score model. When compared to the high-risk group (HRG), the PFS and OS of the low-risk group (LRG) were found to be considerable. Additionally, a better prognosis was found considerably associated with the ESTIMATE score of the patients as well as immune cells infiltration. Our analysis of AS events in LUAD not only helps to clarify the tumorigenesis mechanism of AS but also provides ideas for revealing potential prognostic biomarkers and therapeutic targets. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12890-021-01776-0. BioMed Central 2021-12-06 /pmc/articles/PMC8647402/ /pubmed/34872548 http://dx.doi.org/10.1186/s12890-021-01776-0 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://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
Wang, Gongjun
Qi, Weiwei
Shen, Liwei
Wang, Shasha
Xiao, Ruoxi
Li, Wenqian
Zhang, Yuqi
Bian, Xiaoqian
Sun, Libin
Qiu, Wensheng
The pattern of alternative splicing in lung adenocarcinoma shows novel events correlated with tumorigenesis and immune microenvironment
title The pattern of alternative splicing in lung adenocarcinoma shows novel events correlated with tumorigenesis and immune microenvironment
title_full The pattern of alternative splicing in lung adenocarcinoma shows novel events correlated with tumorigenesis and immune microenvironment
title_fullStr The pattern of alternative splicing in lung adenocarcinoma shows novel events correlated with tumorigenesis and immune microenvironment
title_full_unstemmed The pattern of alternative splicing in lung adenocarcinoma shows novel events correlated with tumorigenesis and immune microenvironment
title_short The pattern of alternative splicing in lung adenocarcinoma shows novel events correlated with tumorigenesis and immune microenvironment
title_sort pattern of alternative splicing in lung adenocarcinoma shows novel events correlated with tumorigenesis and immune microenvironment
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8647402/
https://www.ncbi.nlm.nih.gov/pubmed/34872548
http://dx.doi.org/10.1186/s12890-021-01776-0
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