High SIRT1 expression and low DBC1 expression are associated with poor prognosis in colorectal cancer

Kikuchi, Keiji; Noguchi, Akira; Takahashi, Hiroyuki; Zheng, Hauchaun; Kameda, Yoichi; Sekiguchi, Hironobu; Amaki, Makoto; Miyagi, Yohei; Takano, Yasuo

doi:10.7243/2049-7962-2-1

Cited by 5 publications

(3 citation statements)

References 40 publications

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“…This result is in agreement with previous findings by Cha et al, 32 Stenzinger et al, 33 and Kikuchi et al, 34 who reported that SIRT1 expression was associated with poor survival in various human cancers. SIRT1 is known to deacetylate the major tumor regulators such as P53, FOXO3a, and HIC1, 35 thereby allowing defective DNA to bypass the cell cycle, escape apoptosis, and lead to tumor formation.…”

Section: Discussionsupporting

confidence: 95%

Overexpression of SIRT1 is Associated With Poor Outcomes in Patients With Ovarian Carcinoma

Mvunta

Miyamoto²,

Asaka³

et al. 2017

Applied Immunohistochemistry &Amp; Molecular Morphology

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Sirtuin 1 (SIRT1), originally identified as a longevity gene, regulates DNA repair and metabolism by deacetylating target proteins such as p53. SIRT1 plays a key role in the pathophysiology of metabolic diseases and neurodegenerative disorders, and is considered to protect against age-related diseases including cancer. In contrast, SIRT1 may be oncogenic because its overexpression has been detected in many cancers. The aim of the present study was to clarify the expression and the role of SIRT1 in ovarian carcinoma (OvCa). The expression of SIRT1 was evaluated immunohistochemically in 16 cases of normal ovaries, 35 cases of endometriosis with/without carcinoma, and 68 cases of OvCa (endometrioid, 16; clear cell, 20; mucinous, 16; serous, 16). Staining results were evaluated semiquantitatively by the Immunoreactive Scoring System, and the relationships with clinicopathologic features and outcomes of patients were analyzed. The expression of SIRT1 was higher in endometrioid, mucinous, and clear-cell carcinomas than in the inclusion cysts of normal ovaries, but not in serous carcinoma (P=0.038). The expression of SIRT1 on OvCa did not correlate with age, stage, location of metastasis, or capsular penetration. However, elevated SIRT1 expression was a significant predictor of shorter survival in univariate (P=0.038) and multivariate (P=0.037) survival analyses, regardless of the tumor stage. Results of the present study suggest a positive role for SIRT1 in the development of OvCa and its potential as a novel therapeutic target.

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Section: Discussionsupporting

confidence: 95%

Overexpression of SIRT1 is Associated With Poor Outcomes in Patients With Ovarian Carcinoma

Mvunta

Miyamoto²,

Asaka³

et al. 2017

Applied Immunohistochemistry &Amp; Molecular Morphology

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“…Also, the expression and function of DBC1 within various malignancies were not yet confirmed. And, the cutoff scores for DBC1 expression in present studies are significant incongruity 4,22 ,36-37. Despite there was no critical error in our data extraction and statistical analysis, the phenomena described above may lead to differences in results.…”

Section: Discussionmentioning

confidence: 53%

Deleted in Breast Cancer 1 as a Novel Prognostic Biomarker for Digestive System Cancers: A Meta-Analysis

Liu

Meng

et al. 2019

J. Cancer

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Deleted in Breast Cancer 1 (DBC1/CCAR2) is a regulatory protein involved in cell survival and cancer progression. Herein, we focused on summarizing the overall prognostic value of DBC1 for digestive system cancers. Therefore, we conducted a meta-analysis based on 9 studies with 2391 patients to generated combined hazard ratios (HR) or odds ratio (OR) with its 95% confidence intervals (CI) for overall survival (OS) and clinicopathological features. Positive DBC1 expression was significantly associated with poor OS of digestive system cancers (pooled HR=1.650, 95% CI=1.087-2.504, P<0.019). Stratified analysis also verified the potential prognostic prediction of DBC1 in some subgroups, such as digestive tract cancers (pooled HR=1.685, 95% CI=1.013-2.802, P=0.044), univariate analysis method (pooled HR=2.077, 95%CI=1.221-3.533, P=0.007), publication date within five years (pooled HR=1.609, 95%CI=1.097-2.358, P =0.015), study sample size smaller than 200 (pooled HR=2.304, 95%CI=1.716-3.093, P<0.001) and cutoff value for positive tumor cells more than 50% (pooled HR=1.944, 95% CI=1.479-2.556, P<0.001). Additionally, in terms of the association between DBC1 expression and clinicopathological characteristics, DBC1 expression was correlated to age (pooled OR=0.596, 95%CI =0.467-0.761, P<0.001), WHO classification (pooled OR =3.780, 95% CI=2.303-6.205, P <0.001), Lauren classification (pooled OR=2.000, 95%CI =1.492-2.680, P<0.001), and lymph node metastasis (pooled OR=0.405, 95%CI=0.203-0.806, P=0.010). In conclusion, DBC1 could not only be an independent prognostic factor for survival of patients with digestive system cancer, but might also be a novel target for cancer therapy.

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“…If we simply assume that SIRT1 is a tumor promoter, whereas DBC1 a tumor suppressor counteracting SIRT1, the relative abundance of SIRT1 to that of DBC1 should be elevated in cancers. However, we previously reported that the above simple assumption was not valid in colon cancer [ 30 ]. Excessive SIRT1 activity due to low DBC1 expression might be unfavorable for cancer cell growth.…”

Section: Discussionmentioning

confidence: 99%

SIRT1 expression is associated with a poor prognosis, whereas DBC1 is associated with favorable outcomes in gastric cancer

et al. 2014

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Clinical trials of histone deacetylase (HDAC) inhibitors as antitumor therapy have been conducted for gastric cancer. Expression of SIRT1, a class III HDAC, is related to poor prognosis in some malignancies. We investigated the correlation between SIRT1 expression and progression and prognosis of gastric cancers comparing with molecules linked to SIRT1 in order to better predict the efficacy of HDAC inhibitors in treating this disease. We evaluated SIRT1 expression by western blot in 51 cases and SIRT1, DBC1, acetylated H4K16 (H4K16Ac), acetylated H3K9 (H3K9Ac), and p53 by immunohistochemistry (IHC) in 557 cases of gastric cancer. Western blotting showed that SIRT1 high expression related with statistics to advanced tumor progression, positive lymphatic invasion, positive venous invasion, and advanced stage but not to poor prognosis. IHC revealed that SIRT1 high expression correlated with worse clinico-pathological prognostic factors as same as in western blotting and related poor prognosis both by univariate and multivariate analyses. By the contrast, DBC1 and H4K16Ac were related to favorable prognostic factors and linked to favorable prognosis by univariate analysis but not by multivariate analysis. H3K16Ac correlated only favorable prognostic factors. Results of p53 were very similar to those of SIRT1. We found that SIRT1 high expression closely correlates with progression and prognosis in gastric cancer patients. And it was also indicated that SIRT1 acts as an oncogene by the results of DBC1, H4K16Ac, and H3K9Ac and might be a target molecule of HDAC inhibitor treatment for gastric cancer patients.

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High SIRT1 expression and low DBC1 expression are associated with poor prognosis in colorectal cancer

Cited by 5 publications

References 40 publications

Overexpression of SIRT1 is Associated With Poor Outcomes in Patients With Ovarian Carcinoma

Overexpression of SIRT1 is Associated With Poor Outcomes in Patients With Ovarian Carcinoma

Deleted in Breast Cancer 1 as a Novel Prognostic Biomarker for Digestive System Cancers: A Meta-Analysis

SIRT1 expression is associated with a poor prognosis, whereas DBC1 is associated with favorable outcomes in gastric cancer

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