AB200. SIRT1 expression is elevated in human prostate cancer

Objective: Sirtuin-1 (SIRT1) is a mammalian homolog of the yeast Sir2 deacetylase among class III histone deacetylases that play a vital role in regulation of genome stability and expression. SIRT1 can directly interact with apoptotic proteins, including p53, BAX, and members of the FOXO family of transcription factors. Recent studies suggest that the antiapoptotic effects of SIRT1 may paradoxically increase the risk of cancer development and the targeted inhibition of SIRT1 can effectively limit cancer progression. In cancer cell lines and genetically modified mice, high expression of SIRT1 in human tumors (e.g., breast, colon, lung, and skin) was also reported. Our recent studies on prostate cancer cell lines showed in vitro evidence that SIRT1 may function as a transcriptional co-repressor in the prostate specific antigen promoter and promote prostate tumorigenesis during aging. The present study further investigated SIRT1 expression in human prostate cancer.

Methods: All the tissues made for the tissue microarray were retrieved from the archived paraffin blocks in the department of pathology in the Affiliated Drum Tower Hospital of Nanjing University Medical School. The SIRT1 immunostain was carried out in human prostate cancer tissue microarray that consisted of prostate cancer (PCa, 107 cases), and benign prostate tissue (BPT, 42 cases). PCa cases were divided into 5 groups according to Gleason scores. Groups 1-4 had Gleason score 6 (n=29), 7 (n=20), 8 (n=46), and 9 (n=12), respectively. Fisher’s exact and nonparametric correlation tests were used for statistical analysis.

Results: SIRT1 immunoreactivity significantly increased in PCa (88%, 94/107), compared to that in BPT (29%, 12/42) (P=0). Among the immunopositive PCa cases, SIRT1 expression was observed in 66% (19/29), 100% (20/20), 93% (43/46), 100% (12/12) of cases for Groups 1 through 4, respectively, with significant differences in immunoreactivity among the groups (P=0.001); in addition, SIRT1 immunoreactivity and Gleason scores were significantly correlated (r=0.328; P=0.001). There was no significant difference of AR immunoreactivity between in PCa (68%, 73/107) and in BPT (55%, 23/42) (P=0.122), and SIRT1 immunoreactivity was not significantly correlated with AR immunoreactivity.

Conclusions: SIRT1 expression was significantly increased in human PCa and correlated with Gleason scores. These results suggest that SIRT1 may function as a tumor promoter in human PCa and could be considered as a potential therapeutic target for PCa.

Keywords: Prostate cancer; sirtuin-1 (SIRT1)