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

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.