The Human Cytomegalovirus US31 Gene Predicts Favorable Survival and Regulates the Tumor Microenvironment in Gastric Cancer

Human cytomegalovirus (HCMV) is an oncogenic virus associated with tumorigenesis. Our previous study revealed that the HCMV US31 gene interacted with NF-κB2 and mediated inflammation through macrophages. However, there are few reports on the role of US31 in gastric cancer (GC). The aim of this study...

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Main Authors: Sisi Ye, Yuanbo Hu, Chenbin Chen, Sian Chen, Xinya Tong, Huanbo Zhu, Bo Deng, Xianjing Hu, Xiangwei Sun, Xiaodong Chen, Xinyu Shi, Ruihong Gu, Wangkai Xie, Gangqiang Guo, Dong Xing, Xian Shen, Xiangyang Xue, Shurong Shen
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-04-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2021.614925/full
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author Sisi Ye
Sisi Ye
Yuanbo Hu
Yuanbo Hu
Chenbin Chen
Chenbin Chen
Sian Chen
Sian Chen
Xinya Tong
Huanbo Zhu
Huanbo Zhu
Bo Deng
Xianjing Hu
Xianjing Hu
Xiangwei Sun
Xiangwei Sun
Xiaodong Chen
Xiaodong Chen
Xinyu Shi
Ruihong Gu
Wangkai Xie
Wangkai Xie
Gangqiang Guo
Dong Xing
Xian Shen
Xiangyang Xue
Xiangyang Xue
Shurong Shen
author_facet Sisi Ye
Sisi Ye
Yuanbo Hu
Yuanbo Hu
Chenbin Chen
Chenbin Chen
Sian Chen
Sian Chen
Xinya Tong
Huanbo Zhu
Huanbo Zhu
Bo Deng
Xianjing Hu
Xianjing Hu
Xiangwei Sun
Xiangwei Sun
Xiaodong Chen
Xiaodong Chen
Xinyu Shi
Ruihong Gu
Wangkai Xie
Wangkai Xie
Gangqiang Guo
Dong Xing
Xian Shen
Xiangyang Xue
Xiangyang Xue
Shurong Shen
author_sort Sisi Ye
collection DOAJ
description Human cytomegalovirus (HCMV) is an oncogenic virus associated with tumorigenesis. Our previous study revealed that the HCMV US31 gene interacted with NF-κB2 and mediated inflammation through macrophages. However, there are few reports on the role of US31 in gastric cancer (GC). The aim of this study was to investigate the expression of the US31 gene in GC tissue and assess its role in the occurrence and development of GC. US31 expression in 573 cancer tissues was analyzed using immunohistochemistry. Results showed that US31 was significantly associated with tumor size (P = 0.005) and distant metastasis (P < 0.001). Higher US31 expression indicated better overall survival in GC patients. Overexpression of US31 significantly inhibited the proliferation, migration, and invasion of GC cells in vitro (P < 0.05). Furthermore, expression levels of CD4, CD66b, and CD166 were positively correlated with US31, suggesting that it was involved in regulating the tumor immune microenvironment of GC. RNA sequencing, along with quantitative real-time polymerase chain reaction, confirmed that the expression of US31 promoted immune activation and secretion of inflammatory cytokines. Overall, US31 inhibited the malignant phenotype and regulated tumor immune cell infiltration in GC; these results suggest that US31 could be a potential prognostic factor for GC and may open the door for a new immunotherapy strategy.
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spelling doaj.art-af24cc098df84291a5a1b6b95acb9e4a2022-12-21T22:25:26ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-04-011110.3389/fonc.2021.614925614925The Human Cytomegalovirus US31 Gene Predicts Favorable Survival and Regulates the Tumor Microenvironment in Gastric CancerSisi Ye0Sisi Ye1Yuanbo Hu2Yuanbo Hu3Chenbin Chen4Chenbin Chen5Sian Chen6Sian Chen7Xinya Tong8Huanbo Zhu9Huanbo Zhu10Bo Deng11Xianjing Hu12Xianjing Hu13Xiangwei Sun14Xiangwei Sun15Xiaodong Chen16Xiaodong Chen17Xinyu Shi18Ruihong Gu19Wangkai Xie20Wangkai Xie21Gangqiang Guo22Dong Xing23Xian Shen24Xiangyang Xue25Xiangyang Xue26Shurong Shen27Department of Medical Microbiology and Immunology, Wenzhou Medical University, Wenzhou, ChinaDepartment of Precision Medical Center Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Medical Microbiology and Immunology, Wenzhou Medical University, Wenzhou, ChinaDepartment of Gastrointestinal Surgery, Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Medical Microbiology and Immunology, Wenzhou Medical University, Wenzhou, ChinaDepartment of Gastrointestinal Surgery, Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Medical Microbiology and Immunology, Wenzhou Medical University, Wenzhou, ChinaDepartment of Gastrointestinal Surgery, Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Medical Microbiology and Immunology, Wenzhou Medical University, Wenzhou, ChinaDepartment of Medical Microbiology and Immunology, Wenzhou Medical University, Wenzhou, ChinaDepartment of Gastrointestinal Surgery, Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Medical Microbiology and Immunology, Wenzhou Medical University, Wenzhou, ChinaDepartment of Medical Microbiology and Immunology, Wenzhou Medical University, Wenzhou, ChinaDepartment of Gastrointestinal Surgery, Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Medical Microbiology and Immunology, Wenzhou Medical University, Wenzhou, ChinaDepartment of Gastrointestinal Surgery, Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Medical Microbiology and Immunology, Wenzhou Medical University, Wenzhou, ChinaDepartment of Gastrointestinal Surgery, Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Medical Microbiology and Immunology, Wenzhou Medical University, Wenzhou, ChinaDepartment of Medical Microbiology and Immunology, Wenzhou Medical University, Wenzhou, ChinaDepartment of Medical Microbiology and Immunology, Wenzhou Medical University, Wenzhou, ChinaDepartment of Gastrointestinal Surgery, Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Medical Microbiology and Immunology, Wenzhou Medical University, Wenzhou, ChinaDepartment of Medical Microbiology and Immunology, Wenzhou Medical University, Wenzhou, ChinaDepartment of Gastrointestinal Surgery, Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Medical Microbiology and Immunology, Wenzhou Medical University, Wenzhou, ChinaDepartment of Gastrointestinal Surgery, Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaWenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Zhejiang Chinese Medical University, Wenzhou, ChinaHuman cytomegalovirus (HCMV) is an oncogenic virus associated with tumorigenesis. Our previous study revealed that the HCMV US31 gene interacted with NF-κB2 and mediated inflammation through macrophages. However, there are few reports on the role of US31 in gastric cancer (GC). The aim of this study was to investigate the expression of the US31 gene in GC tissue and assess its role in the occurrence and development of GC. US31 expression in 573 cancer tissues was analyzed using immunohistochemistry. Results showed that US31 was significantly associated with tumor size (P = 0.005) and distant metastasis (P < 0.001). Higher US31 expression indicated better overall survival in GC patients. Overexpression of US31 significantly inhibited the proliferation, migration, and invasion of GC cells in vitro (P < 0.05). Furthermore, expression levels of CD4, CD66b, and CD166 were positively correlated with US31, suggesting that it was involved in regulating the tumor immune microenvironment of GC. RNA sequencing, along with quantitative real-time polymerase chain reaction, confirmed that the expression of US31 promoted immune activation and secretion of inflammatory cytokines. Overall, US31 inhibited the malignant phenotype and regulated tumor immune cell infiltration in GC; these results suggest that US31 could be a potential prognostic factor for GC and may open the door for a new immunotherapy strategy.https://www.frontiersin.org/articles/10.3389/fonc.2021.614925/fullhuman cytomegalovirusgastric cancerUS31tumor immune microenvironmentprognostic factor
spellingShingle Sisi Ye
Sisi Ye
Yuanbo Hu
Yuanbo Hu
Chenbin Chen
Chenbin Chen
Sian Chen
Sian Chen
Xinya Tong
Huanbo Zhu
Huanbo Zhu
Bo Deng
Xianjing Hu
Xianjing Hu
Xiangwei Sun
Xiangwei Sun
Xiaodong Chen
Xiaodong Chen
Xinyu Shi
Ruihong Gu
Wangkai Xie
Wangkai Xie
Gangqiang Guo
Dong Xing
Xian Shen
Xiangyang Xue
Xiangyang Xue
Shurong Shen
The Human Cytomegalovirus US31 Gene Predicts Favorable Survival and Regulates the Tumor Microenvironment in Gastric Cancer
Frontiers in Oncology
human cytomegalovirus
gastric cancer
US31
tumor immune microenvironment
prognostic factor
title The Human Cytomegalovirus US31 Gene Predicts Favorable Survival and Regulates the Tumor Microenvironment in Gastric Cancer
title_full The Human Cytomegalovirus US31 Gene Predicts Favorable Survival and Regulates the Tumor Microenvironment in Gastric Cancer
title_fullStr The Human Cytomegalovirus US31 Gene Predicts Favorable Survival and Regulates the Tumor Microenvironment in Gastric Cancer
title_full_unstemmed The Human Cytomegalovirus US31 Gene Predicts Favorable Survival and Regulates the Tumor Microenvironment in Gastric Cancer
title_short The Human Cytomegalovirus US31 Gene Predicts Favorable Survival and Regulates the Tumor Microenvironment in Gastric Cancer
title_sort human cytomegalovirus us31 gene predicts favorable survival and regulates the tumor microenvironment in gastric cancer
topic human cytomegalovirus
gastric cancer
US31
tumor immune microenvironment
prognostic factor
url https://www.frontiersin.org/articles/10.3389/fonc.2021.614925/full
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