The Expression And Significance Of ABCC5 In Hepatocellular Carcinoma Based On Bioinformatics Analysis And RT-PCR Technology

Background: Hepatocellular carcinoma(HCC)is the most common subtype of liver cancer.Many patients with HCC are diagnosed at an advanced stage,which is related to their early symptoms.Currently,including surgical resection,interventional therapy,liver transplantation has been widely used in the treatment of hepatocellular carcinoma,in recent years the rise of immunotherapy and targeted therapy is also a promising direction,but because of its poor prognosis and higher mortality suggests the existing tumor markers effect is not ideal,so looking for new diagnostic markers of hepatocellular carcinoma and explore its role in hepatocellular carcinoma immune microenvironment is of great value.In recent years,with the rapid development of bioinformatic technology,chip and high-throughput sequencing technology and widely application,accumulated more and more genomics data in the field of tumor research,these databases for the research of biology,laid the foundation for clinical treatment,ABCC5 is an ATP binding box transporter can mediate cyclic nucleotide or nucleotide analogues across membrane,it can combine and ATP hydrolysis for the transportation of various substrates.Related studies have found that ABCC5 is poorly expressed in many normal tissues,but has increased mRNA levels in lung,colon,pancreatic,and breast cancer tissues.Therefore,it is important to explore the expression of ABCC5 in pan-carcinoma and its progression in hepatocellular carcinoma.Objective: To test the expression level of ABCC5 in pan-cancer and normal tissues,and to investigate the effect and prognosis of ABCC5 expression in liver cancer progression.Methods: The expression of ABCC5 in pan cancer was searched through TIMER2.0and Oncomine database and the prognostic value in pan cancer;the expression level of ABCC5 in HCC and normal tissues was analyzed based on TCGA database.According to the expression of ABCC5 in HCC,the survival package in R software was used to analyze the relationship between gene expression and prognosis survival,and to analyze the correlation with pathological characteristics.Next,independent prognostic factors for predicting HCC survival were predicted using both univariate and multivariate Cox analysis.We used the CIBERSORT algorithm to explore the immunity of ABCC5 in the tumor microenvironment(TME)of liver cancer.The "GSVA" package was used to explore the pathways mainly enriched in low ABCC5 expression.Finally,the expression of ABCC5 mRNA in HCC and adjacent control group was verified by qRT-PCR.And according to its expression situation,combined with the clinicopathological analysis of the correlation.Results:1.Through TIMER2.0 database and Oncomine database,ABCC5 was up-regulated in10 tumors,including HCC,and was related to the poor prognosis of hepatocellular carcinoma patients;2.Mapping the univariate and multivariate analysis suggests that ABCC5 can be an independent factor affecting the poor prognosis of hepatocellular carcinoma(HCC).3.The diagnostic value of this gene in HCC was assessed by drawing the ROC and PRC curves.The AUC under the ROC curve was 0.929 and the AUC was 0.990 under the PRC curve,suggesting that this gene may be a good potential diagnostic marker for HCC.4.Immune infiltration analysis revealed that ABCC5 expression was related to memory B cells,CD8 + T cells,CD4 memory-activated T cells,T cell follicular helper,T cell regulation(Tregs)and macrophage M0;5.Through GSVA enrichment analysis,it was found that the genes in the ABCC5 overexpression group were mainly enriched in cell cycle-related pathways,such as the HALLMARK?E2F?TARGETS HALLMARK?G2M?CHECKPOINT pathway,which play an important role in the occurrence and development of HCC.6.The qRT-PCR results verified the high expression of ABCC5 mRNA in HCC;the high and low ABCC5 mRNA expression and pathological characteristics analysis suggested that ABCC5 is related to TNM stage(P<0.05).Conclusion:1.ABCC5 gene expression is upregulated in hepatocellular carcinoma and is associated with poor prognosis of hepatocellular carcinoma,which is an independent influencing factor of its poor prognosis;2.ABCC5 is of great value for the diagnosis of HCC and can be used as a potential diagnostic marker of HCC;3.ABCC5 is associated with the infiltration,differentiation,and cell cycle of some immune cells of HCC.