SIRT1 Expression Is Associated with Good Prognosis in Colorectal Cancer

ABSTRACT

BACKGROUND: Silent mating type information regulation 2 homolog 1 (SIRT1), an NAD+-dependent deacetylase, might act as a tumor promoter by inhibiting p53, but may also as a tumor suppressor by inhibiting several oncogenes such as beta-catenin and survivin. Deleted in breast cancer 1 (DBC1) is known as a negative regulator of SIRT1. METHODS: Immunohistochemical expressions of SIRT1, DBC1, beta-catenin, surviving, and p53 were evaluated using 2 mm tumor cores from 349 colorectal cancer patients for tissue microarray. RESULTS: Overexpression of SIRT1, DBC1, survivin, and p53 was seen in 235 (67%), 183 (52%), 193 (55%), and 190 (54%) patients, respectively. Altered expression of beta-catenin was identified in 246 (70%) patients. On univariate analysis, overexpression of SIRT1 (p=0.029) and altered expression of beta-catenin (p=0.008) were significantly associated with longer overall survival. Expression of SIRT1 was significantly related to DBC1 (p=0.001), beta-catenin (p=0.001), and survivin (p=0.002), but not with p53. On multivariate analysis, age, tumor stage, differentiation, and expression of SIRT1 were independent prognostic factors significantly associated with overall survival. CONCLUSIONS: SIRT1 overexpression is a good prognostic factor for colorectal cancer, and SIRT1 may interact with beta-catenin and survivin rather than p53.