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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2021
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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. |
format | Online Article Text |
id | pubmed-8647402 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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