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Systematic Profiling of Alternative Splicing for Sarcoma Patients Reveals Novel Prognostic Biomarkers Associated with Tumor Microenvironment and Immune Cells

BACKGROUND: Alternative splicing (AS) events is a novel biomarker of tumor prognosis, but the role of AS events in sarcoma patients remains unclear. MATERIAL/METHODS: RNA-seq and clinicopathologic data of the sarcoma cohort were extracted from the TCGA database and data on AS events were downloaded...

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Autores principales: Hu, Chuan, Wang, Yuanhe, Liu, Chuan, Shen, Rui, Chen, Bo, Sun, Kang, Rao, Huili, Ye, Lin, Ye, Jianjun, Tian, Shaoqi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388651/
https://www.ncbi.nlm.nih.gov/pubmed/32683393
http://dx.doi.org/10.12659/MSM.924126
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author Hu, Chuan
Wang, Yuanhe
Liu, Chuan
Shen, Rui
Chen, Bo
Sun, Kang
Rao, Huili
Ye, Lin
Ye, Jianjun
Tian, Shaoqi
author_facet Hu, Chuan
Wang, Yuanhe
Liu, Chuan
Shen, Rui
Chen, Bo
Sun, Kang
Rao, Huili
Ye, Lin
Ye, Jianjun
Tian, Shaoqi
author_sort Hu, Chuan
collection PubMed
description BACKGROUND: Alternative splicing (AS) events is a novel biomarker of tumor prognosis, but the role of AS events in sarcoma patients remains unclear. MATERIAL/METHODS: RNA-seq and clinicopathologic data of the sarcoma cohort were extracted from the TCGA database and data on AS events were downloaded from the TCGASpliceSeq database. Univariate Cox analysis, LASSO regression analysis, and multivariate Cox analysis were performed to determine the overall survival (OS)- and disease-free survival (DFS)-related AS events. Two nomograms were developed based on the independent variables, and subgroup analysis was performed. The area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the nomograms. Then, we used the CIBERSORT and ESTIMATE package to determine the immune cell proportion and tumor microenvironment (TME) score, respectively. The associations between AS events-based clusters and TME and immune cells were studied. RESULTS: We identified 1945 and 1831 AS events as OS- and DFS-related AS events, respectively. Two nomograms based on the AS events and clinical data were established and the AUCs of nomograms ranged from 0.807 to 0.894. The calibration curve and DCA showed excellent performance of nomograms. In addition, the results indicated the distinct relationships between AS events-based clusters and OS, DFS, immune score, stromal score, and 10 immune cells. CONCLUSIONS: Our study indicated that AS events are novel prognostic biomarkers for sarcoma patients that may be associated with the TME and immune cells.
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spelling pubmed-73886512020-08-05 Systematic Profiling of Alternative Splicing for Sarcoma Patients Reveals Novel Prognostic Biomarkers Associated with Tumor Microenvironment and Immune Cells Hu, Chuan Wang, Yuanhe Liu, Chuan Shen, Rui Chen, Bo Sun, Kang Rao, Huili Ye, Lin Ye, Jianjun Tian, Shaoqi Med Sci Monit Database Analysis BACKGROUND: Alternative splicing (AS) events is a novel biomarker of tumor prognosis, but the role of AS events in sarcoma patients remains unclear. MATERIAL/METHODS: RNA-seq and clinicopathologic data of the sarcoma cohort were extracted from the TCGA database and data on AS events were downloaded from the TCGASpliceSeq database. Univariate Cox analysis, LASSO regression analysis, and multivariate Cox analysis were performed to determine the overall survival (OS)- and disease-free survival (DFS)-related AS events. Two nomograms were developed based on the independent variables, and subgroup analysis was performed. The area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the nomograms. Then, we used the CIBERSORT and ESTIMATE package to determine the immune cell proportion and tumor microenvironment (TME) score, respectively. The associations between AS events-based clusters and TME and immune cells were studied. RESULTS: We identified 1945 and 1831 AS events as OS- and DFS-related AS events, respectively. Two nomograms based on the AS events and clinical data were established and the AUCs of nomograms ranged from 0.807 to 0.894. The calibration curve and DCA showed excellent performance of nomograms. In addition, the results indicated the distinct relationships between AS events-based clusters and OS, DFS, immune score, stromal score, and 10 immune cells. CONCLUSIONS: Our study indicated that AS events are novel prognostic biomarkers for sarcoma patients that may be associated with the TME and immune cells. International Scientific Literature, Inc. 2020-07-19 /pmc/articles/PMC7388651/ /pubmed/32683393 http://dx.doi.org/10.12659/MSM.924126 Text en © Med Sci Monit, 2020 This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) )
spellingShingle Database Analysis
Hu, Chuan
Wang, Yuanhe
Liu, Chuan
Shen, Rui
Chen, Bo
Sun, Kang
Rao, Huili
Ye, Lin
Ye, Jianjun
Tian, Shaoqi
Systematic Profiling of Alternative Splicing for Sarcoma Patients Reveals Novel Prognostic Biomarkers Associated with Tumor Microenvironment and Immune Cells
title Systematic Profiling of Alternative Splicing for Sarcoma Patients Reveals Novel Prognostic Biomarkers Associated with Tumor Microenvironment and Immune Cells
title_full Systematic Profiling of Alternative Splicing for Sarcoma Patients Reveals Novel Prognostic Biomarkers Associated with Tumor Microenvironment and Immune Cells
title_fullStr Systematic Profiling of Alternative Splicing for Sarcoma Patients Reveals Novel Prognostic Biomarkers Associated with Tumor Microenvironment and Immune Cells
title_full_unstemmed Systematic Profiling of Alternative Splicing for Sarcoma Patients Reveals Novel Prognostic Biomarkers Associated with Tumor Microenvironment and Immune Cells
title_short Systematic Profiling of Alternative Splicing for Sarcoma Patients Reveals Novel Prognostic Biomarkers Associated with Tumor Microenvironment and Immune Cells
title_sort systematic profiling of alternative splicing for sarcoma patients reveals novel prognostic biomarkers associated with tumor microenvironment and immune cells
topic Database Analysis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388651/
https://www.ncbi.nlm.nih.gov/pubmed/32683393
http://dx.doi.org/10.12659/MSM.924126
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