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 β-catenin and survivin. Deleted in breast cancer 1 (DBC1) is known as a negative regulator of SIRT1.

Methods: Immunohistochemical expressions of SIRT1, DBC1, β-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 β-catenin was identified in 246 (70%) patients. On univariate analysis, overexpression of SIRT1 (p=0.029) and altered expression of β-catenin (p=0.008) were significantly associated with longer overall survival. Expression of SIRT1 was significantly related to DBC1 (p=0.001), β-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 β-catenin and survivin rather than p53.

Keywords: Adenocarcinoma; Beta catenin; Colon; DBC1; SIRT1.

Fig. 1

Immunohistochemical expression of silent mating type information regulation 2 homolog 1 (SIRT1), deleted in breast cancer 1 (DBC1), β-catenin, survivin, and p53 in normal colorectal mucosa and colorectal cancer. Normal colorectal mucosa shows SIRT1 expression with weak nuclear staining. DBC1 and survivin are expressed in all of the normal mucosa with moderate to strong intensity. β-catenin shows membranous staining pattern in normal colorectal mucosa. p53 is not expressed in normal mucosa (left panel). Representative figures of positive and negative expression of SIRT, DBC1, β-catenin, survivin, and p53 in adenocarcinoma are shown (middle and right panel, respectively).