Decreased mitochondrial SIRT3 expression is a potential molecular biomarker associated with poor outcome in breast cancer.
Decreased mitochondrial SIRT3 expression is a potential molecular biomarker associated with poor outcome in breast cancer.
复制标题
线粒体SIRT3表达降低是与乳腺癌预后不良相关的潜在分子生物标志物。
DOI：
10.1016/j.humpath.2014.01.004
复制
发表时间：
2014-05
期刊：
影响因子：
3.3
通讯作者：
Abdulkadir SA
中科院分区：
文献类型：
--
作者：
Desouki MM;Doubinskaia I;Gius D;Abdulkadir SA
SIRT 3是基因组表达的线粒体定位的肿瘤抑制蛋白，其中它通过使下游蛋白质底物脱乙酰化来指导多个代谢过程。小鼠中Sirt 3的遗传缺失导致从一年开始的乳腺肿瘤的自发发展，并且已经在包括乳腺恶性肿瘤在内的几种人类肿瘤中观察到SIRT 3 mRNA的降低。在这项研究中，我们评估了SIRT 3在人乳腺癌组织芯片中的表达，并研究了SIRT 3表达与乳腺癌患者预后之间的关系。与正常乳腺上皮相比，SIRT 3蛋白在肿瘤中的表达显著较低，包括与肿瘤相邻的正常上皮。SIRT 3表达最低四分位数的乳腺癌患者具有显著更短的局部无复发生存期[风险比= 0.53（0.47-0.61），对数秩p=0]。值得注意的是，SIRT 3低表达与所有分析的乳腺癌亚型（包括ER+、ER-、HER 2+和基础亚型）的局部无复发生存率降低相关（风险比=0.44至0.65;对数秩p=0至0.0019）。这些结果突出了SIRT 3作为乳腺癌中肿瘤抑制蛋白的重要性，并表明SIRT 3可能是一种潜在的分子生物标志物，用于识别所有乳腺癌分子亚型的高风险患者。
SIRT3 is a genomically expressed, mitochondrial localized tumor suppressor protein where it directs multiple metabolic processes by deacetylating downstream protein substrates. Genetic deletion of Sirt3 in mice leads to the spontaneous development of mammary tumors starting at one year and decreased SIRT3 mRNA has been observed in several human tumors including breast malignancies. In this investigation we assessed SIRT3 expression in human breast cancer tissue microarray and examined the relationship between SIRT3 expression and outcome in breast cancer patients. SIRT3 protein expression is significantly lower in neoplastic compared to normal breast epithelium, including normal epithelium adjacent to tumors. Breast cancer patients in the lowest quartile of SIRT3 expression had a significantly shorter locoregional relapse free survival [Hazard ratio = 0.53 (0.47–0.61), log rank p=0]. Notably, low SIRT3 expression was associated with reduced locoregional relapse-free survival in all breast cancer subtypes analyzed, including ER+, ER−, HER2+, and basal subtypes (Hazard ratios =0.44 to 0.65; log rank p=0 to 0.0019). These results highlight the importance of the SIRT3 as a tumor suppressor protein in breast cancer and suggest that SIRT3 may be a potential molecular biomarker to identify high risk patients across all molecular subtypes of breast cancer.