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.
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.
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.
SIRT1 overexpression is a good prognostic factor for colorectal cancer, and SIRT1 may interact with β-catenin and survivin rather than p53.
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Sirtuin 1 (SIRT1) and deleted in breast cancer 1 (DBC1) are known as tumor suppressor or promoter genes. This may be due to their diverse functions and interaction with other proteins. Gastric adenocarcinoma is one of the most common malignancies, but little is known about its carcinogenesis. Therefore, we investigated the association of immunohistochemical expression of SIRT1, DBC1, p53, and β-catenin and their variable clinicopathological characteristics.
We obtained samples from 452 patients who underwent gastrectomy. Tissue microarray blocks were constructed and immonohistochemical staining was performed.
Expression of DBC1 and SIRT1 was associated with lower histologic grade, intestinal type of Lauren classification, and lower pT (p<0.001) and pN stage (DBC1, p=0.002; SIRT1, p<0.001). Association between absence of lymphatic invasion, and SIRT1 (p=0.001) and DBC1 (p=0.004) was observed. Cytoplasmic β-catenin expression was associated with lower histologic grade, pT, pN, tumor-node-metastasis (TNM) stage, DBC1 (p<0.001), and SIRT1 (p=0.001). Expression of SIRT1 and DBC1 was not associated with p53 (p=0.063 and p=0.060). DBC1 was an independent good prognostic factor in multivariate analysis (p=0.012).
SIRC1 and DBC1 can be considered to be good prognostic factors in gastric adenocarcinoma.
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