Survival-associated alternative splicing events interact with the immune microenvironment in stomach adenocarcinoma

Alternative splicing (AS) increases the diversity of mRNA during transcription; it might play a role in alteration of the immune microenvironment, which could influence the development of immunotherapeutic strategies against cancer.BACKGROUNDAlternative splicing (AS) increases the diversity of mRNA...

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Published inWorld journal of gastroenterology : WJG Vol. 27; no. 21; pp. 2871 - 2894
Main Authors Ye, Zai-Sheng, Zheng, Miao, Liu, Qin-Ying, Zeng, Yi, Wei, Sheng-Hong, Wang, Yi, Lin, Zhi-Tao, Shu, Chen, Zheng, Qiu-Hong, Chen, Lu-Chuan
Format Journal Article
LanguageEnglish
Published Baishideng Publishing Group Inc 07.06.2021
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Clinical and Translational Research
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Abstract Alternative splicing (AS) increases the diversity of mRNA during transcription; it might play a role in alteration of the immune microenvironment, which could influence the development of immunotherapeutic strategies against cancer.BACKGROUNDAlternative splicing (AS) increases the diversity of mRNA during transcription; it might play a role in alteration of the immune microenvironment, which could influence the development of immunotherapeutic strategies against cancer.To obtain the transcriptomic and clinical features and AS events in stomach adenocarcinoma (STAD) from the database. The overall survival data associated with AS events were used to construct a signature prognostic model for STAD.AIMTo obtain the transcriptomic and clinical features and AS events in stomach adenocarcinoma (STAD) from the database. The overall survival data associated with AS events were used to construct a signature prognostic model for STAD.Differentially expressed immune-related genes were identified between subtypes on the basis of the prognostic model. In STAD, 2042 overall-survival-related AS events were significantly enriched in various pathways and influenced several cellular functions. Furthermore, the network of splicing factors and overall-survival-associated AS events indicated potential regulatory mechanisms underlying the AS events in STAD.METHODSDifferentially expressed immune-related genes were identified between subtypes on the basis of the prognostic model. In STAD, 2042 overall-survival-related AS events were significantly enriched in various pathways and influenced several cellular functions. Furthermore, the network of splicing factors and overall-survival-associated AS events indicated potential regulatory mechanisms underlying the AS events in STAD.An eleven-AS-signature prognostic model (CD44|14986|ES, PPHLN1|21214|AT, RASSF4|11351|ES, KIAA1147|82046|AP, PPP2R5D|76200|ES, LOH12CR1|20507|ES, CDKN3|27569|AP, UBA52|48486|AD, CADPS|65499|AT, SRSF7| 53276|RI, and WEE1|14328|AP) was constructed and significantly related to STAD overall survival, immune cells, and cancer-related pathways. The differentially expressed immune-related genes between the high- and low-risk score groups were significantly enriched in cancer-related pathways.RESULTSAn eleven-AS-signature prognostic model (CD44|14986|ES, PPHLN1|21214|AT, RASSF4|11351|ES, KIAA1147|82046|AP, PPP2R5D|76200|ES, LOH12CR1|20507|ES, CDKN3|27569|AP, UBA52|48486|AD, CADPS|65499|AT, SRSF7| 53276|RI, and WEE1|14328|AP) was constructed and significantly related to STAD overall survival, immune cells, and cancer-related pathways. The differentially expressed immune-related genes between the high- and low-risk score groups were significantly enriched in cancer-related pathways.This study provided an AS-related prognostic model, potential mechanisms for AS, and alterations in the immune microenvironment (immune cells, genes, and pathways) for future research in STAD.CONCLUSIONThis study provided an AS-related prognostic model, potential mechanisms for AS, and alterations in the immune microenvironment (immune cells, genes, and pathways) for future research in STAD.
AbstractList Alternative splicing (AS) increases the diversity of mRNA during transcription; it might play a role in alteration of the immune microenvironment, which could influence the development of immunotherapeutic strategies against cancer.BACKGROUNDAlternative splicing (AS) increases the diversity of mRNA during transcription; it might play a role in alteration of the immune microenvironment, which could influence the development of immunotherapeutic strategies against cancer.To obtain the transcriptomic and clinical features and AS events in stomach adenocarcinoma (STAD) from the database. The overall survival data associated with AS events were used to construct a signature prognostic model for STAD.AIMTo obtain the transcriptomic and clinical features and AS events in stomach adenocarcinoma (STAD) from the database. The overall survival data associated with AS events were used to construct a signature prognostic model for STAD.Differentially expressed immune-related genes were identified between subtypes on the basis of the prognostic model. In STAD, 2042 overall-survival-related AS events were significantly enriched in various pathways and influenced several cellular functions. Furthermore, the network of splicing factors and overall-survival-associated AS events indicated potential regulatory mechanisms underlying the AS events in STAD.METHODSDifferentially expressed immune-related genes were identified between subtypes on the basis of the prognostic model. In STAD, 2042 overall-survival-related AS events were significantly enriched in various pathways and influenced several cellular functions. Furthermore, the network of splicing factors and overall-survival-associated AS events indicated potential regulatory mechanisms underlying the AS events in STAD.An eleven-AS-signature prognostic model (CD44|14986|ES, PPHLN1|21214|AT, RASSF4|11351|ES, KIAA1147|82046|AP, PPP2R5D|76200|ES, LOH12CR1|20507|ES, CDKN3|27569|AP, UBA52|48486|AD, CADPS|65499|AT, SRSF7| 53276|RI, and WEE1|14328|AP) was constructed and significantly related to STAD overall survival, immune cells, and cancer-related pathways. The differentially expressed immune-related genes between the high- and low-risk score groups were significantly enriched in cancer-related pathways.RESULTSAn eleven-AS-signature prognostic model (CD44|14986|ES, PPHLN1|21214|AT, RASSF4|11351|ES, KIAA1147|82046|AP, PPP2R5D|76200|ES, LOH12CR1|20507|ES, CDKN3|27569|AP, UBA52|48486|AD, CADPS|65499|AT, SRSF7| 53276|RI, and WEE1|14328|AP) was constructed and significantly related to STAD overall survival, immune cells, and cancer-related pathways. The differentially expressed immune-related genes between the high- and low-risk score groups were significantly enriched in cancer-related pathways.This study provided an AS-related prognostic model, potential mechanisms for AS, and alterations in the immune microenvironment (immune cells, genes, and pathways) for future research in STAD.CONCLUSIONThis study provided an AS-related prognostic model, potential mechanisms for AS, and alterations in the immune microenvironment (immune cells, genes, and pathways) for future research in STAD.
Author Liu, Qin-Ying
Wang, Yi
Ye, Zai-Sheng
Zheng, Miao
Zheng, Qiu-Hong
Chen, Lu-Chuan
Shu, Chen
Zeng, Yi
Lin, Zhi-Tao
Wei, Sheng-Hong
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Author contributions: Ye ZS designed the project, analyzed data, prepared figures, and wrote the manuscript; Chen LC conceived the study, supervised the results, critically revised/wrote the manuscript, and was responsible for its financial support and the corresponding works; all the other authors conceived the study, and critically revised the manuscript; all authors approved the final manuscript, Ye ZS, Zheng M, Zeng Y, Wei SH and Liu QY contributed equally to the work.
Supported by the National Clinical Key Specialty Construction Program of China and Grants from the National Science Foundation Project of the Fujian Science and Technology Department, No. 2017J01264 and No. 2018Y0015; the Foundation for Fujian Provincial Health Technology Project, No. 2019-ZQN-16, No. 2019-CXB-9, and No. 2019006; and the Startup Fund for Scientific Research, Fujian Medical University, No. 2017Q1219 and No. 2017Q1220.
Corresponding author: Lu-Chuan Chen, BM BCh, MD, Chief Doctor, Director, Surgical Oncologist, Department of Gastrointestinal Surgical Oncology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, No. 420 Fuma Road, Jin’an District, Fuzhou 350014, Fujian Province, China. luchuanchen@fjzlhospital.com
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Title Survival-associated alternative splicing events interact with the immune microenvironment in stomach adenocarcinoma
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