Clinicopathological significance of SIRT1 expression in colorectal adenocarcinoma.

Abstract

Sirtuin 1 (SIRT1) has been reported to have diverse roles in various biological processes through deacetylation of histone and nonhistone proteins. However, the correlations between SIRT1 protein expression, clinicopathological parameters, and survival of colorectal cancer patients remain unclear. SIRT1 protein expression in a paraffin-embedded tissue microarray, including 13 benign adenomas, nine liver metastasis tissues, and 120 paired colorectal cancer and normal mucosa tissues, was measured by immunohistochemistry. SIRT1 mRNA and protein expression in colon cancer cell lines with different metastatic potential and normal colon cells were detected by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. The correlations between SIRT1 protein expression, clinicopathological features, and prognosis were analyzed. All samples (100 %) were positive for SIRT1, with variable staining in the cytoplasm rather than the nucleus. There was significant difference in SIRT1 overexpression between adenocarcinomas and normal mucosal tissues (P < 0.01, χ(2) test). SIRT1 overexpression was more frequently observed in advanced-stage tumors and lymph node or liver metastases (P = 0.046, 0.002, and 0.004, respectively, χ(2) test). SIRT1 expression was also significantly elevated in the more aggressive colon cancer cell line SW620. SIRT1 overexpression was significantly correlated with poor overall survival (P = 0.013, log-rank test) and disease-free survival (P = 0.012, log-rank test). SIRT1 overexpression was correlated with advanced-stage and poor prognosis. SIRT1 may play an important role in the progression of colorectal cancer.