2. Department of Pathology, School of Medicine, Kitasato University, Sagamihara, Kanagawa, Japan.
3. Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang, Liaoning, China.
4. Department of Pathology, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan.
5. Department of Laboratory Medicine, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan.
6. Department of Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan.
Background: SIRT1 deacetylates various cellular proteins in addition to histones and functions as an either tumor-promoter or tumor-suppressor. The participation of SIRT1 in colorectal cancer onset and progression remains controversial. SIRT1 activity is regulated among the others by deleted in breast cancer 1 (DBC1). We asked if the expression of the SIRT1-inhibitor DBC1 affects contribution of SIRT1 to colorectal cancer.
Methods: We examined the expression of SIRT1 and DBC1 in 114 cancers by immunohistochemical staining (IHC) and Western blot analysis (WB) of proteins extracted from tissues. In 55 cancers where the results of IHC and WB are consistent, we analyzed correlations with clinico-pathological features and prognosis of the patients.
Results: High expression of SIRT1 and DBC1 was observed in 8 and 12 cases, respectively. High SIRT1 expression expression was significantly associated with shorter patients survival specifically in cases with low DBC1 expression.
Conclusions: High expression of SIRT1 and low expression of its inhibitor DBC1 associate with poor prognosis in colorectal cancer patients.tended to positively correlated with poor patient prognosis, while high DBC1 expression correlated with poor differentiation. Multivariate analysis showed high SIRT1 expression can be an independent marker for poor patient prognosis. While expressions of SIRT1 and DBC1 were coordinatedly elevated in cancers, high SIRT1
Keywords: colorectal cancer, SIRT1, DBC1, prognosis