Study On The Mechanism Of Poor Prognosis In Patients With Colorectal Cancer Caused By Downregulation Of B3GNT6 Expression

Background: The B3GNT6 protein is a member of the O-Glc NAc transferase(OGT)family and is responsible for the production of the core3 structure of O-glycans.It is generally expressed in the gastrointestinal(GI)tract;however,its clinical significance in colorectal cancer remains largely unexplored.Objective: To investigate the effect of low expression of B3GNT6 protein and m RNA in colorectal cancer on the prognosis of patients with colorectal cancer.To explore the potential mechanism of low expression of B3GNT6 on the prognosis of patients with colorectal cancer.Materials and Methods: We obtained m RNA transcriptomic sequencing data from 3 gene expression omnibus(Gene Expression Omnibus,GEO)datasets(GSE37182,GSE39582,GSE103512)and The Cancer Genome Atlas(The Cancer Genome Atlas,TCGA)to compare the B3GNT6 m RNA levels between colorectal cancer and normal tissues and further evaluate its value as a prognostic marker in colorectal cancer.Bioinformatics analysis is used to determine the biological response related to expression level of B3GNT6.The samples from our own cohort were used for immunohistochemical staining,and the protein expression level was verified in combination with the Human Protein Atlas database.Results: B3GNT6 expression was significantly downregulated in colorectal cancer tissues as compared to that in normal tissues at both m RNA and protein levels.Survival analysis indicated that downregulation of B3GNT6 m RNA expression was associated with poor overall survival in patients with colorectal cancer.Low B3GNT6 m RNA levels were significantly associated with chromosome instability(CIN)and KRAS mutations in patients with colorectal cancer.Gene set enrichment analysis(GSEA)revealed that low B3GNT6 expression levels in colorectal cancer were associated with increased proteasome activity.Conclusions: The results of this study demonstrate that low expression of B3GNT6 is a potential biomarker for poor outcomes in patients with CRC.Its functional mechanisms may be diverse,including more frequent activation of KRAS/ERK signal pathways,chromosome instability and so on.These novel findings may prove helpful for molecular diagnosis and provide a new therapeutic target for colorectal cancer.