Expression And Function Of CCDC6 In Hepatobiliary Carcinoma

Background:Hepatobiliary carcinoma is consisted of Hepatocellular carcinoma(HCC)and Cholangiocarcinoma(CCA),taking up the first and the second most common hepatobiliary malignancy,respectively.CCDC6(Coiled-coil domain containing 6 protein)is one kind of protein that interacts with apoptosis and DNA damage response and is commonly detected in cells.However,the prognostic and biological roles of CCDC6 in hepatobiliary carcinoma remain largely unknown.Methods:UALCAN,GEPIA,TIMER,GeneMANIA,STRING and HPA were used to determine the prognostic values and biological function of CCDC6 in HCC and CCA.The original online data were downloaded from TCGA and GEO databases and integrated via R 3.2.2.Patients’ groups including 94 HCC and 99 iCCA in our hospital were also applied to verify the relation between CCDC6 and hepatobiliary carcinoma using immunohistochemistry.KEGG,GO and GESA were also used to investigate relative pathways of CCDC6 in HCC.The correlations between CCDC6 expression and tumor-infiltrated immune cells were analyzed via the TIMER and GEPIA databases.The relationships between CCDC6 and marker genes of tumor-infiltrated immune cells in HCC were analyzed for confirmation.Results:The mRNA and protein expression patterns of CCDC6 members were noticeably upregulated in HCC and CCA compared to normal tissue.The high expression levels of CCDC6 were significantly correlated with higher tumor grades as well as poor prognosis in HCC patients,in contrast to none significations for CCA.Functional enrichment analysis revealed that CCDC6 were mainly involved in histone acetylation,cell cycle process,gene transcription,as well as several immune cell-related pathways.Furthermore,the expression levels of CCDC6 were positively correlated with the activities of tumor-infiltrating immune cells,including Macrophages,CD4+T Cells and Dendritic Cells.Conclusion:In summary,CCDC6 with high expression contributes to the poor prognosis of HCC patients.It might be developed as a therapeutic target and prognostic indicator for HCC in targeting therapy and immunotherapy.