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Summary Aims Recently, the important role of silent mating type information regulation 2 homolog 1 (SIRT1) and deleted in breast cancer 1 (DBC1) in human cancer has been extensively studied and their role has been closely related with the control of P53 and androgen receptor (AR) functions. However, their role in clear cell renal cell carcinoma (CRCC) is still unknown. Methods We evaluated the expression of SIRT1, P53, acetylated-P53, DBC1 and AR and their prognostic significance in 200 CRCC patients. Results The expression of SIRT1, P53, DBC1, and AR significantly correlated with each other and all of them predicted shorter overall survival (OS), relapse-free survival (RFS), and cancer-specific survival (CSS). In contrast, the expression of acetylated-P53 predicted favourable OS, RFS, and CSS. Combined expression pattern of acetylated-P53 and P53 (Ac-P53/P53) also closely correlated with survival of CRCC patients. Multivariate analysis revealed DBC1, acetylated-P53, and Ac-P53/P53 expression as independent prognostic indicators for OS and RFS, and Ac-P53 expression as an independent prognostic indicator for CSS. Conclusions This study demonstrates that the acetylation status of P53 and the expression of SIRT1, DBC1, and AR could be new prognostic indicators for CRCC and suggest that SIRT1-P53 and DBC1-AR related pathways could be new therapeutic targets for the treatment of CRCC.

After intramembranous proteolysis-mediated loss of the extracellular domain of the epithelial cell adhesion molecule (EpEx) and release of an intracellular domain (EpICD) into the cytoplasm, EpICD sequentially associates with FHL2 to form a nuclear complex with beta-catenin and Lef-1. This association induces gene transcription involved in the activation of the oncogenic potential of epithelial cell adhesion molecule (EpCAM). We examined the localization and expression of EpEx, EpICD and beta-catenin in surgical specimens of extrahepatic cholangiocarcinoma (ECC) from 79 patients. There was a significant correlation between the nuclear expression of EpICD and beta-catenin in ECC tissues. Frequent nuclear co-localization of EpICD and beta-cate-nin was observed in cancer cells forming the invasive front. Forced overexpression of EpICD in the CC cells significantly increased the cell growth and proliferation. The overexpression of EpICD in the CC cells also increased the expression levels of the active form of beta-catenin and EpCAM target genes. Furthermore, the over-expression of EpICD significantly enhanced the migration and invasiveness of CC cells. Conversely, inhibition of EpCAM by siRNA significantly decreased the CC cell proliferation, migration and invasion. These results indicate that spatial localization of EpICD and its mutual interaction with beta-catenin may be important in ECC progression and invasion.