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
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DOI：
10.1097/pai.0000000000000316
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发表时间：
2017-07-01
影响因子：
1.6
通讯作者：
Shiozawa, Tanri
中科院分区：
文献类型：
--
作者：
Mvunta, David H.;Miyamoto, Tsutomu;Shiozawa, Tanri
Sirtuin 1 （SIRT1）最初被认为是一种长寿基因，它通过使p53等靶蛋白去乙酰化来调节DNA修复和代谢。SIRT1在代谢性疾病和神经退行性疾病的病理生理中起关键作用，并被认为可以预防包括癌症在内的年龄相关疾病。相反，SIRT1可能是致癌的，因为它的过表达已经在许多癌症中被检测到。本研究的目的是阐明SIRT1在卵巢癌（OvCa）中的表达及其作用。免疫组织化学法检测了16例正常卵巢、35例伴有/不伴有癌的子宫内膜异位症和68例OvCa（子宫内膜样16例、透明细胞20例、粘液样16例、浆液样16例）中SIRT1的表达。采用免疫反应评分系统对染色结果进行半定量评价，并分析其与患者临床病理特征及转归的关系。SIRT1在子宫内膜样癌、黏液性癌和透明细胞癌中的表达高于正常卵巢包涵性囊肿，但在浆液性癌中表达不高（P=0.038）。SIRT1在OvCa上的表达与年龄、分期、转移位置或包膜穿透无关。然而，无论肿瘤分期如何，在单因素（P=0.038）和多因素（P=0.037）生存分析中，SIRT1表达升高是缩短生存期的重要预测因子。本研究的结果表明SIRT1在OvCa的发展中发挥积极作用，并有可能成为一种新的治疗靶点。
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.