Systemic Analysis of RNA Alternative Splicing Signals Related to the Prognosis for Head and Neck Squamous Cell Carcinoma

Alternative splicing (AS) is an important mechanism that is responsible for the production of protein diversity. An increasing body of evidence has suggested that out-of-control AS is closely related to the genesis and development of cancer. Systematic analysis of genome-wide AS in head and neck squ...

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Main Authors: Zhexuan Li, Xun Chen, Ming Wei, Guancheng Liu, Yongquan Tian, Xin Zhang, Gangcai Zhu, Changhan Chen, Jiangyi Liu, Tiansheng Wang, Gongbiao Lin, Juncheng Wang, Gengming Cai, Yunxia Lv
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-02-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fonc.2020.00087/full
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author Zhexuan Li
Xun Chen
Ming Wei
Guancheng Liu
Yongquan Tian
Xin Zhang
Gangcai Zhu
Changhan Chen
Jiangyi Liu
Tiansheng Wang
Gongbiao Lin
Juncheng Wang
Gengming Cai
Yunxia Lv
author_facet Zhexuan Li
Xun Chen
Ming Wei
Guancheng Liu
Yongquan Tian
Xin Zhang
Gangcai Zhu
Changhan Chen
Jiangyi Liu
Tiansheng Wang
Gongbiao Lin
Juncheng Wang
Gengming Cai
Yunxia Lv
author_sort Zhexuan Li
collection DOAJ
description Alternative splicing (AS) is an important mechanism that is responsible for the production of protein diversity. An increasing body of evidence has suggested that out-of-control AS is closely related to the genesis and development of cancer. Systematic analysis of genome-wide AS in head and neck squamous cell carcinoma (HNSCC) has not yet been carried out, and consideration of this topic remains at the preliminary stage and requires further investigation. In this study, systemic bioinformatic analysis was carried out on the genome-wide AS events of 555 clinical HNSCC samples from the TCGA database. Firstly, we statistically analyzed the distributions of seven AS event types in HNSCC samples. Then, through univariate survival analysis, we observed the relationship between AS and the prognosis of the disease and found that 437 intersections of AS events were significantly related to overall survival. Among them, 335 cross-genes showed a high degree of consistency in the genes associated with overall survival and recurrence. The overall survival was significantly related to AS events. Besides, the frequency of overall survival-related ES events was evidently reduced, while the AP and the AT events were increased. In addition, AT events accounted for the largest proportion. Further, multiple regression model analysis proved that AS could become a new classification method for HNSCC, and KEGG enrichment analysis proved that most genes and proteins interacting with AS events had different biological functions and were associated with a variety of diseases. Finally, through the selection of characteristic HNSCC genes and the construction of a prognostic model, seven cross-genes related to survival and recurrence were screened out, and these characteristic genes were verified by multivariate survival model analysis so as to classify the prognosis at different splicing times and gene expression levels. These results have laid a solid foundation for our further research and play a decisive role in showing the correlation of AS with the prognosis of HNSCC.
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spelling doaj.art-31fd08401fa341ebb265fbb2332bf4ec2022-12-22T01:06:45ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-02-011010.3389/fonc.2020.00087490390Systemic Analysis of RNA Alternative Splicing Signals Related to the Prognosis for Head and Neck Squamous Cell CarcinomaZhexuan Li0Xun Chen1Ming Wei2Guancheng Liu3Yongquan Tian4Xin Zhang5Gangcai Zhu6Changhan Chen7Jiangyi Liu8Tiansheng Wang9Gongbiao Lin10Juncheng Wang11Gengming Cai12Yunxia Lv13Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Stomatology, First Affiliated Hospital of Quanzhou, Fujian Medical University, Quanzhou, ChinaDepartment of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Otolaryngology Head and Neck Surgery, Affiliated Hospital of Guilin Medical University, Guilin, ChinaDepartment of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Otolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, ChinaQuanzhou Disease Prevention and Control Center, Quanzhou, ChinaDepartment of Otolaryngology Head and Neck Surgery, The Third Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Otolaryngology Head and Neck Surgery, First Affiliated Hospital of Quanzhou, Fujian Medical University, Quanzhou, ChinaDepartment of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Otolaryngology Head and Neck Surgery, First Affiliated Hospital of Quanzhou, Fujian Medical University, Quanzhou, ChinaDepartment of Thyroid Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaAlternative splicing (AS) is an important mechanism that is responsible for the production of protein diversity. An increasing body of evidence has suggested that out-of-control AS is closely related to the genesis and development of cancer. Systematic analysis of genome-wide AS in head and neck squamous cell carcinoma (HNSCC) has not yet been carried out, and consideration of this topic remains at the preliminary stage and requires further investigation. In this study, systemic bioinformatic analysis was carried out on the genome-wide AS events of 555 clinical HNSCC samples from the TCGA database. Firstly, we statistically analyzed the distributions of seven AS event types in HNSCC samples. Then, through univariate survival analysis, we observed the relationship between AS and the prognosis of the disease and found that 437 intersections of AS events were significantly related to overall survival. Among them, 335 cross-genes showed a high degree of consistency in the genes associated with overall survival and recurrence. The overall survival was significantly related to AS events. Besides, the frequency of overall survival-related ES events was evidently reduced, while the AP and the AT events were increased. In addition, AT events accounted for the largest proportion. Further, multiple regression model analysis proved that AS could become a new classification method for HNSCC, and KEGG enrichment analysis proved that most genes and proteins interacting with AS events had different biological functions and were associated with a variety of diseases. Finally, through the selection of characteristic HNSCC genes and the construction of a prognostic model, seven cross-genes related to survival and recurrence were screened out, and these characteristic genes were verified by multivariate survival model analysis so as to classify the prognosis at different splicing times and gene expression levels. These results have laid a solid foundation for our further research and play a decisive role in showing the correlation of AS with the prognosis of HNSCC.https://www.frontiersin.org/article/10.3389/fonc.2020.00087/fullhead and neck squamous cell carcinoma (HNSCC)TCGA databaseprognosisAlternative Splicing (AS)oncology
spellingShingle Zhexuan Li
Xun Chen
Ming Wei
Guancheng Liu
Yongquan Tian
Xin Zhang
Gangcai Zhu
Changhan Chen
Jiangyi Liu
Tiansheng Wang
Gongbiao Lin
Juncheng Wang
Gengming Cai
Yunxia Lv
Systemic Analysis of RNA Alternative Splicing Signals Related to the Prognosis for Head and Neck Squamous Cell Carcinoma
Frontiers in Oncology
head and neck squamous cell carcinoma (HNSCC)
TCGA database
prognosis
Alternative Splicing (AS)
oncology
title Systemic Analysis of RNA Alternative Splicing Signals Related to the Prognosis for Head and Neck Squamous Cell Carcinoma
title_full Systemic Analysis of RNA Alternative Splicing Signals Related to the Prognosis for Head and Neck Squamous Cell Carcinoma
title_fullStr Systemic Analysis of RNA Alternative Splicing Signals Related to the Prognosis for Head and Neck Squamous Cell Carcinoma
title_full_unstemmed Systemic Analysis of RNA Alternative Splicing Signals Related to the Prognosis for Head and Neck Squamous Cell Carcinoma
title_short Systemic Analysis of RNA Alternative Splicing Signals Related to the Prognosis for Head and Neck Squamous Cell Carcinoma
title_sort systemic analysis of rna alternative splicing signals related to the prognosis for head and neck squamous cell carcinoma
topic head and neck squamous cell carcinoma (HNSCC)
TCGA database
prognosis
Alternative Splicing (AS)
oncology
url https://www.frontiersin.org/article/10.3389/fonc.2020.00087/full
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