SIRT1表达与结直肠癌的良好预后相关。

SIRT1 Expression Is Associated with Good Prognosis in Colorectal Cancer.

作者信息

Jung Wonkyung, Hong Kwang Dae, Jung Woon Yong, Lee Eunjung, Shin Bong Kyung, Kim Han Kyeom, Kim Aeree, Kim Baek-Hui

机构信息

Department of Pathology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea.

出版信息

Korean J Pathol. 2013 Aug;47(4):332-9. doi: 10.4132/KoreanJPathol.2013.47.4.332. Epub 2013 Aug 26.

DOI:10.4132/KoreanJPathol.2013.47.4.332

PMID:24009628

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3759632/

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.

摘要

背景

沉默交配型信息调节因子2同源物1（SIRT1）是一种依赖烟酰胺腺嘌呤二核苷酸（NAD+）的去乙酰化酶，可能通过抑制p53发挥肿瘤促进作用，但也可能通过抑制β-连环蛋白和生存素等多种癌基因发挥肿瘤抑制作用。乳腺癌缺失基因1（DBC1）是已知的SIRT1负调节因子。

方法

使用来自349例结直肠癌患者的2毫米肿瘤组织芯构建组织芯片，评估SIRT1、DBC1、β-连环蛋白、生存素和p53的免疫组化表达。

结果

分别在235例（67%）、183例（52%）、193例（55%）和190例（54%）患者中观察到SIRT1、DBC1、生存素和p53的过表达。在246例（70%）患者中发现β-连环蛋白表达改变。单因素分析显示，SIRT1过表达（p=0.029）和β-连环蛋白表达改变（p=0.008）与总生存期延长显著相关。SIRT1的表达与DBC1（p=0.001）、β-连环蛋白（p=0.001）和生存素（p=0.002）显著相关，但与p53无关。多因素分析显示，年龄、肿瘤分期、分化程度和SIRT1表达是与总生存期显著相关的独立预后因素。