Clinical and Translational Research
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2021; 27(21): 2871-2894
Published online Jun 7, 2021. doi: 10.3748/wjg.v27.i21.2871
Survival-associated alternative splicing events interact with the immune microenvironment in stomach adenocarcinoma
Zai-Sheng Ye, Miao Zheng, Qin-Ying Liu, Yi Zeng, Sheng-Hong Wei, Yi Wang, Zhi-Tao Lin, Chen Shu, Qiu-Hong Zheng, Lu-Chuan Chen
Zai-Sheng Ye, Yi Zeng, Sheng-Hong Wei, Yi Wang, Zhi-Tao Lin, Chen Shu, Lu-Chuan Chen, Department of Gastrointestinal Surgical Oncology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou 350014, Fujian Province, China
Miao Zheng, Department of Clinical Laboratory, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou 350001, Fujian Province, China
Qin-Ying Liu, Qiu-Hong Zheng, Department of Fujian Provincial Key Laboratory of Tumor Biotherapy, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou 350014, Fujian Province, China
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.
Institutional review board statement: The manuscript used data from TCGA database, which is a common database. The Institutional review board statement was not addressed in this article.
Clinical trial registration statement: The manuscript used data from TCGA database, which is a common database. The Clinical trial registration statement was not addressed in this article.
Informed consent statement: The manuscript used data from TCGA database, which is a common database. The Informed consent statement was not addressed in this article.
Conflict-of-interest statement: The authors have declared that no competing interests exist.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
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
Received: December 24, 2020
Peer-review started: December 25, 2020
First decision: January 17, 2021
Revised: January 23, 2021
Accepted: April 9, 2021
Article in press: April 9, 2021
Published online: June 7, 2021
Abstract
BACKGROUND

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.

AIM

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

Keywords: Stomach adenocarcinoma, Alternative splicing, Tumor microenvironment, Immune-related genes and pathways

Core Tip: In this study, we performed a systematic analysis of prognostic splicing events in stomach adenocarcinoma (STAD), constructed an elevated Alternative splicing (AS)-signature prognostic model, and explored the association between AS and cancer immunity. The final overall survival-related AS events, differentially expressed immune-related genes, and the enriched pathways may play an important role in tumorigenesis in STAD; they deserve further study in clinical applications as diagnostic biomarkers and therapeutic targets.