CHSY3 promotes proliferation and migration in gastric cancer and is associated with immune infiltration

Abstract Background The glycosyltransferase CHSY3 is a CHSY family member, yet its importance in the context of gastric cancer development remains incompletely understood. The present study was thus developed to explore the mechanistic importance of CHSY3 as a regulator of gastric cancer. Methods Ex...

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Main Authors: Xinkun Huang, Yonghui Liu, Chenyu Qian, Qicheng Shen, Menglong Wu, Bin Zhu, Ying Feng
Format: Article
Language:English
Published: BMC 2023-07-01
Series:Journal of Translational Medicine
Subjects:
Online Access:https://doi.org/10.1186/s12967-023-04333-x
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author Xinkun Huang
Yonghui Liu
Chenyu Qian
Qicheng Shen
Menglong Wu
Bin Zhu
Ying Feng
author_facet Xinkun Huang
Yonghui Liu
Chenyu Qian
Qicheng Shen
Menglong Wu
Bin Zhu
Ying Feng
author_sort Xinkun Huang
collection DOAJ
description Abstract Background The glycosyltransferase CHSY3 is a CHSY family member, yet its importance in the context of gastric cancer development remains incompletely understood. The present study was thus developed to explore the mechanistic importance of CHSY3 as a regulator of gastric cancer. Methods Expression of CHSY3 was verified by TCGA, GEO and HPA databases. Kaplan–Meier curve, ROC, univariate cox, multivariate cox, and nomogram models were used to verify the prognostic impact and predictive value of CHSY3. KEGG and GO methods were used to identify signaling pathways associated with CHSY3. TIDE and IPS scores were used to assess the immunotherapeutic value of CHSY3. WGCNA, Cytoscape constructs PPI networks and random forest models to identify key Hub genes. Finally, qRT-PCR and immunohistochemical staining were performed to verify CHSY3 expression in clinical specimens. The ability of CHSY3 to regulate tumor was further assessed by CCK-8 assay and cloning assay, EDU assay, migration assay, invasion assay, and xenograft tumor model analysis. Results The expression of CHSY3 was discovered to be abnormally upregulated in GC tissues through TCGA, GEO, and HPA databases, and the expression of CHSY3 was associated with poor prognosis in GC patients. Correlation analysis and Cox regression analysis revealed higher CHSY3 expression in higher T staging, an independent prognostic factor for GC. Moreover, elevated expression of CHSY3 was found to reduce the benefit of immunotherapy as assessed by the TIDE score and IPS score. Then, utilizing WGCNA, the PPI network constructed by Cytoscape, and random forest model, the Hub genes of COL5A2, POSTN, COL1A1, and FN1 associated with immunity were screened. Finally, the expression of CHSY3 in GC tissues was verified by qRT-PCR and immunohistochemical staining. Moreover, the expression of CHSY3 was further demonstrated by in vivo and in vitro experiments to promote the proliferation, migration, and invasive ability of GC. Conclusions The results of this study suggest that CHSY3 is an important regulator of gastric cancer progression, highlighting its promise as a therapeutic target for gastric cancer.
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spelling doaj.art-d0f6b4d8de104c21b228e62507f0bafd2023-07-23T11:25:20ZengBMCJournal of Translational Medicine1479-58762023-07-0121112010.1186/s12967-023-04333-xCHSY3 promotes proliferation and migration in gastric cancer and is associated with immune infiltrationXinkun Huang0Yonghui Liu1Chenyu Qian2Qicheng Shen3Menglong Wu4Bin Zhu5Ying Feng6Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong UniversityDepartment of Laboratory Medicine, Nanjing Zhongda Hospital, School of Medicine, Southeast UniversityDepartment of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong UniversityDepartment of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong UniversityDepartment of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong UniversityDepartment of General Surgery, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical SchoolDepartment of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong UniversityAbstract Background The glycosyltransferase CHSY3 is a CHSY family member, yet its importance in the context of gastric cancer development remains incompletely understood. The present study was thus developed to explore the mechanistic importance of CHSY3 as a regulator of gastric cancer. Methods Expression of CHSY3 was verified by TCGA, GEO and HPA databases. Kaplan–Meier curve, ROC, univariate cox, multivariate cox, and nomogram models were used to verify the prognostic impact and predictive value of CHSY3. KEGG and GO methods were used to identify signaling pathways associated with CHSY3. TIDE and IPS scores were used to assess the immunotherapeutic value of CHSY3. WGCNA, Cytoscape constructs PPI networks and random forest models to identify key Hub genes. Finally, qRT-PCR and immunohistochemical staining were performed to verify CHSY3 expression in clinical specimens. The ability of CHSY3 to regulate tumor was further assessed by CCK-8 assay and cloning assay, EDU assay, migration assay, invasion assay, and xenograft tumor model analysis. Results The expression of CHSY3 was discovered to be abnormally upregulated in GC tissues through TCGA, GEO, and HPA databases, and the expression of CHSY3 was associated with poor prognosis in GC patients. Correlation analysis and Cox regression analysis revealed higher CHSY3 expression in higher T staging, an independent prognostic factor for GC. Moreover, elevated expression of CHSY3 was found to reduce the benefit of immunotherapy as assessed by the TIDE score and IPS score. Then, utilizing WGCNA, the PPI network constructed by Cytoscape, and random forest model, the Hub genes of COL5A2, POSTN, COL1A1, and FN1 associated with immunity were screened. Finally, the expression of CHSY3 in GC tissues was verified by qRT-PCR and immunohistochemical staining. Moreover, the expression of CHSY3 was further demonstrated by in vivo and in vitro experiments to promote the proliferation, migration, and invasive ability of GC. Conclusions The results of this study suggest that CHSY3 is an important regulator of gastric cancer progression, highlighting its promise as a therapeutic target for gastric cancer.https://doi.org/10.1186/s12967-023-04333-xCHSY3Gastric cancerTIDEIPSPrognosis
spellingShingle Xinkun Huang
Yonghui Liu
Chenyu Qian
Qicheng Shen
Menglong Wu
Bin Zhu
Ying Feng
CHSY3 promotes proliferation and migration in gastric cancer and is associated with immune infiltration
Journal of Translational Medicine
CHSY3
Gastric cancer
TIDE
IPS
Prognosis
title CHSY3 promotes proliferation and migration in gastric cancer and is associated with immune infiltration
title_full CHSY3 promotes proliferation and migration in gastric cancer and is associated with immune infiltration
title_fullStr CHSY3 promotes proliferation and migration in gastric cancer and is associated with immune infiltration
title_full_unstemmed CHSY3 promotes proliferation and migration in gastric cancer and is associated with immune infiltration
title_short CHSY3 promotes proliferation and migration in gastric cancer and is associated with immune infiltration
title_sort chsy3 promotes proliferation and migration in gastric cancer and is associated with immune infiltration
topic CHSY3
Gastric cancer
TIDE
IPS
Prognosis
url https://doi.org/10.1186/s12967-023-04333-x
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