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Updated: Jul 23, 2025
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
CHSY3 promotes proliferation and migration in gastric cancer and is associated with immune infiltration
Xinkun Huang1,2,3, Yonghui Liu4, Chenyu Qian1,5,3
1Department of Gastrointestinal Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, China.
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.
Insights
The glycosyltransferase CHSY3 (CHSY3) is upregulated in gastric cancer, correlating with poor prognosis and reduced immunotherapy benefit. This study identifies CHSY3 as a key regulator of gastric cancer progression and a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Gastric cancer (GC) remains a significant health concern with incompletely understood regulatory mechanisms.
- The role of the glycosyltransferase CHSY3 (CHSY3) in GC development requires further elucidation.
Purpose of the Study:
- To investigate the mechanistic importance of CHSY3 as a regulator of gastric cancer progression.
- To explore CHSY3's prognostic value and potential as a therapeutic target in GC.
Main Methods:
- Bioinformatic analysis of TCGA, GEO, and HPA databases for CHSY3 expression and prognostic value.
- Assessment of CHSY3's impact on immunotherapy response using TIDE and IPS scores.
- Identification of key hub genes using WGCNA, PPI networks, and random forest models.
- In vitro and in vivo experiments to evaluate CHSY3's role in GC cell proliferation, migration, and invasion.
Main Results:
- CHSY3 expression is abnormally upregulated in GC tissues and associated with poor prognosis and higher T staging.
- Elevated CHSY3 expression correlates with reduced immunotherapy benefit.
- CHSY3 promotes GC cell proliferation, migration, and invasion.
- Key hub genes (COL5A2, POSTN, COL1A1, FN1) associated with immunity were identified.
Conclusions:
- CHSY3 is a significant regulator of gastric cancer progression.
- CHSY3 presents a promising therapeutic target for gastric cancer treatment.
