The Expression Of GLYATL1 Gene And Its Potential Role In Patients With Hepatocellular Carcinoma

BackgroundHepatocellular carcinoma(HCC)accounts for the majority of primary liver cancers and is one of the most malignant tumors.Radical or palliative hepatectomy is still the most effective strategy of HCC management.However,the pathogenesis of liver cancer has not yet been elucidated.Therefore,it is urgent to further study the pathogenesis of liver cancer and identify new molecular markers related to hepatocellular carcinoma.Glycine-N-acyltransferase-like 1(GLYATL1),which is involved in the detoxification of endogenous and exogenous acyl-CoA,promotes glutamine metabolism in xenobiotic metabolism.Recent evidence suggests an association between GLYATL1 and tumors,such as prostate cancer and triple negative breast cancer.However,there are few comprehensive analyses of GLYATL1 in HCC.We evaluated the expression and prognostic value of GLYATL1 and explored the mechanism underlying the association between GLYATL1 and HCC.ObjectiveBy using a variety of online databases and immunohistochemistry(IHC)to detect the expression of GLYATL1 in HCC tissues and corresponding adjacent tissues,and further analyze the relationship between its expression and clinicopathological parameters and survival prognosis.In addition,we tried to explore the potential role of GLYATL1 in HCC.MethodsGLYATL1 mRNA expression in HCC was investigated in the Oncomine database and confirmed in the Gene Expression Profiling Interactive Analysis(GEPIA)databases.Secondly,the expression level of GLYATL1 protein in HCC tissues was revealed through The Human Protein Atlas(HPA)and IHC.Thirdly,its prognostic value in different cancers was identified by GEPIA and the clinical information from our cohort.Then,we used our cohort to analyze the correlation between GLYATL1 expression and the clinicopathological characteristics.Then,through STRING database,a protein-protein interaction(PPI)network was constructed.Besides,we use Gene Set Enrichment Analysis(GSEA)to identify significantly enriched pathways.Finally,we explored the correlation between GLYATL1 and genes involved in glutamine metabolism in HCC based on Tumor Immune Estimation Resource(TIMER)database.ResultsBoth Oncomine database and GEPIA database confirmed that the mRNAexpression level of GLYATL1 in HCC was significantly decreased compared with the corresponding adjacent tissues(p<0.05).HPA database and IHC results confirmed that GLYATL1 is mainly expressed in the cytoplasm.Compared with normal liver tissue,the protein expression of GLYATL1 in HCC was significantly decreased(p<0.05).Further survival and prognosis studies have shown that low expression of GLYATL1 is related to the poor prognosis of HCC,and its expression is positively related to differentiation grade,TNM stage,and recurrence status(p<0.05).The PPI network suggested that GLYATL1 is co-expressed with ten genes,including CNGA3 and GNB5.GSEA revealed that GLYATL1 is predominantly negatively enriched in bile acid metabolism,xenobiotic metabolism,fatty acid metabolism,coagulation,the peroxisome and adipogenesis.The expression of GLYATL1 showed a significant association with the expression of most genes involved in mitochondrial glutamine metabolism.ConclusionsThe level of GLYATL1 is down-regulated in HCC tissues and is associated with poor prognosis.It is also related to differentiation grade,TNM stage,and recurrence status.It is expected to be a biomarker for evaluating the prognosis of HCC patients,and can provide an important direction for exploring the mechanism of liver cancer.