CHSY3 As A Potential Therapeutic Target For Gastric Cancer

Abstract

Background: Chondroitin synthase 3(CHSY3) has been reported to be closely related to the occurrence, development, recurrence, and metastasis of a variety of cancers. But its role in gastric cancer (GC) has not been studied. Methods: Tumor Immune Estimate Resource (TIMER), The Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) were used to detect the expression of CHSY3 in gastric cancer. Analyze the correlation between CHSY3 expression and clinicopathological parameters. Draw a Kaplan-Meier survival curve to detect the clinical prognostic significance of CHSY3 in gastric cancer. Meta-analysis of the above results to determine the role of CHSY3 in GC.COX regression analysis was used to study whether CHSY3 is a predictor of GC patients. Analyze the methylation data from the TCGA database to determine the sites with a significant correlation. Through GO analysis and KEGG analysis to study the regulation mechanism of CHSY3 related genes. Screen 3 genes (APOD, GJA1, SERPINE1) from the related genes of CHSY3 as a predictive signature.Constructed a nomogram to predict the 1-year and 3-year survival probability of GC patients. The TIMER database was used to study the correlation between CHSY3 and tumor infiltrating immune cells.Study the drug sensitivity of CHSY3 related genes by using Gene Set Cancer Analysis (GSCA).Results: CHSY3 was highly expressed in GC and significantly correlated with the T stage.The higher the expression level of CHSY3 in GC, the higher the methylation level of cg06610705 and cg11572844,which suggests that patients with gastric cancer have a poorer prognosis.Enrichment analysis identified multiple cancer-related pathways, for example, PI3K-Akt signaling pathway,MAPK signaling pathway, and TGF-beta signaling pathway.The risk score has a very high predictive value.CHSY3 is closely associated with CD4+ T cells, macrophages, neutrophils, and dendritic.Besides,different mutational forms of CHSY3 were associated with the immune infiltration of 6 leukocytes.In addition,CHSY3 may contribute to drug resistance in GC.Conclusion: CHSY3 may be a potential prognostic biomarker for gastric cancer, and it can be used as a new therapeutic target for the treatment of gastric cancer.