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Systematic profiling of alternative splicing in Helicobacter pylori-negative gastric cancer and their clinical significance

BACKGROUND: Alternative splicing (AS) may cause structural and functional variations in the protein to promote the proliferation of tumor cells. However, there is no comprehensive analysis of the clinical significance of AS in Helicobacter pylori-negative gastric cancer (HP(−) GC). METHODS: The clin...

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Autores principales: Liu, Chuan, Hu, Chuan, Li, Zhi, Feng, Jing, Huang, Jiale, Yang, Bowen, Wen, Ti
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325377/
https://www.ncbi.nlm.nih.gov/pubmed/32617077
http://dx.doi.org/10.1186/s12935-020-01368-8
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author Liu, Chuan
Hu, Chuan
Li, Zhi
Feng, Jing
Huang, Jiale
Yang, Bowen
Wen, Ti
author_facet Liu, Chuan
Hu, Chuan
Li, Zhi
Feng, Jing
Huang, Jiale
Yang, Bowen
Wen, Ti
author_sort Liu, Chuan
collection PubMed
description BACKGROUND: Alternative splicing (AS) may cause structural and functional variations in the protein to promote the proliferation of tumor cells. However, there is no comprehensive analysis of the clinical significance of AS in Helicobacter pylori-negative gastric cancer (HP(−) GC). METHODS: The clinical, gene expression profile data and AS events of 138 HP(−) GC patients were obtained from the database named the cancer genome atlas. Differently expressed AS (DEAS) events were determined by a comparison of the PSI values between HP(−) GC samples and adjacent normal samples. Unsupervised clustering analysis, proportional regression and Kaplan–Meier analysis were used to explore the association between clinical data and immune features and to establish two nomograms about the prognosis of HP(−) GC. Finally, splicing networks were constructed using Cytoscape. RESULTS: A total of 48141 AS events and 1041 DEAS events were found in HP(−) GC. Various functions and pathways of DEAS events parent genes were enriched, such as cell-substrate junction, cell leading edge, focal adhension, and AMPK signaling. Seven overall survival (OS)-related and seven disease-free survival (DFS)-related AS events were used to construct the prognostic signatures. Based on the independent prognostic factors, two nomograms were established and showed excellent performance. Then, splicing regulatory networks among the correlations suggested that splicing factors were significantly associated with prognostic DEASs. Finally, the unsupervised clustering analysis revealed that DEAS-based clusters were associated with clinical characteristics, tumor microenvironment, tumor mutation burden, and immune features. CONCLUSION: Seven OS-related and seven DFS-related AS events have been found to be correlated with the prognosis of HP(−) GC and can be used as prognostic factors to establish an effective nomogram.
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spelling pubmed-73253772020-07-01 Systematic profiling of alternative splicing in Helicobacter pylori-negative gastric cancer and their clinical significance Liu, Chuan Hu, Chuan Li, Zhi Feng, Jing Huang, Jiale Yang, Bowen Wen, Ti Cancer Cell Int Primary Research BACKGROUND: Alternative splicing (AS) may cause structural and functional variations in the protein to promote the proliferation of tumor cells. However, there is no comprehensive analysis of the clinical significance of AS in Helicobacter pylori-negative gastric cancer (HP(−) GC). METHODS: The clinical, gene expression profile data and AS events of 138 HP(−) GC patients were obtained from the database named the cancer genome atlas. Differently expressed AS (DEAS) events were determined by a comparison of the PSI values between HP(−) GC samples and adjacent normal samples. Unsupervised clustering analysis, proportional regression and Kaplan–Meier analysis were used to explore the association between clinical data and immune features and to establish two nomograms about the prognosis of HP(−) GC. Finally, splicing networks were constructed using Cytoscape. RESULTS: A total of 48141 AS events and 1041 DEAS events were found in HP(−) GC. Various functions and pathways of DEAS events parent genes were enriched, such as cell-substrate junction, cell leading edge, focal adhension, and AMPK signaling. Seven overall survival (OS)-related and seven disease-free survival (DFS)-related AS events were used to construct the prognostic signatures. Based on the independent prognostic factors, two nomograms were established and showed excellent performance. Then, splicing regulatory networks among the correlations suggested that splicing factors were significantly associated with prognostic DEASs. Finally, the unsupervised clustering analysis revealed that DEAS-based clusters were associated with clinical characteristics, tumor microenvironment, tumor mutation burden, and immune features. CONCLUSION: Seven OS-related and seven DFS-related AS events have been found to be correlated with the prognosis of HP(−) GC and can be used as prognostic factors to establish an effective nomogram. BioMed Central 2020-06-30 /pmc/articles/PMC7325377/ /pubmed/32617077 http://dx.doi.org/10.1186/s12935-020-01368-8 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 Primary Research
Liu, Chuan
Hu, Chuan
Li, Zhi
Feng, Jing
Huang, Jiale
Yang, Bowen
Wen, Ti
Systematic profiling of alternative splicing in Helicobacter pylori-negative gastric cancer and their clinical significance
title Systematic profiling of alternative splicing in Helicobacter pylori-negative gastric cancer and their clinical significance
title_full Systematic profiling of alternative splicing in Helicobacter pylori-negative gastric cancer and their clinical significance
title_fullStr Systematic profiling of alternative splicing in Helicobacter pylori-negative gastric cancer and their clinical significance
title_full_unstemmed Systematic profiling of alternative splicing in Helicobacter pylori-negative gastric cancer and their clinical significance
title_short Systematic profiling of alternative splicing in Helicobacter pylori-negative gastric cancer and their clinical significance
title_sort systematic profiling of alternative splicing in helicobacter pylori-negative gastric cancer and their clinical significance
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325377/
https://www.ncbi.nlm.nih.gov/pubmed/32617077
http://dx.doi.org/10.1186/s12935-020-01368-8
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