| OBJECTIVE: To investigate the expression characteristics,clinical and prognostic significance as well as potential functions of exonuclease 1(EXO1)in liver cancer based on data mining of Genotype-Tissue Expression database(GTEx)and The Cancer Genome Atlas(TCGA)database.METHODS: The expression distribution of EXO1 in normal human cells/tissues/organs was demonstrated by GTEx database.The aberrant expression of EXO1 in pan-cancer and its clinical and prognostic significance was analyzed by the portal websites of TCGA,including UALCAN,GEPIA and c Bio Portal.And the RNA sequencing dataset that consist of paired tumor and adjacent liver tissues from 159 patients were used for independent validation.Based on the TCGA RNA sequencing data of liver cancer,the co-expression genes that were highly correlated with EXO1 expression was obtained.The protein interaction network of EXO1 was constructed by STRING tool,and the gene ontology(GO)and pathway enrichment analyses were performed by Funrich software.RESULTS: EXO1 was mainly expressed in lymphocytes.And it was expressed at low levels in a few tissues/organs,whereas it was barely expressed in most of tissues/organs,including normal liver.In most of cancer types,EXO1 was significantly overexpressed,including liver cancer.The high expression of EXO1 in liver cancer was associated with race,tumor pathological differentiation and clinical staging.Importantly,it was associated with shorter overall survival time and recurrence-free survival time.The results of independent validation were consistent with the TCGA data.The dramatic overexpression of EXO1 in liver cancer tissues was associated with tumor thrombus,higher serum AFP levels,advanced clinical BCLC and TNM staging,as well as shorter overall survival time.DNA copy number amplification and promoter hypomethylation might result in its overexpression in liver cancer.The co-expression gene analysis of EXO1 showed that EXO1 regulates cell cycle progression,DNA replication,DNA damage repair and other biological processes through ATM,ATR,Aurora B and the other signaling pathways,thereby promoting the hepatocarcinogenesis.CONCLUSION: EXO1 is barely expressed in normal liver,but it is overexpressed in tumortissues of liver cancer.It may contribute to carcinogenesis via several biological processes,such as regulation of cell cycle,DNA replication and DNA damage repair,etc.Therefore,EXO1 can serve as a potential diagnostic and prognostic biomarker,as well as a therapeutic intervention target in liver cancer. |
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