Shuang Ting, Wang Min, Zhou Yingying, Shi Cong
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004, China.
Med Oncol. 2015 Dec;32(12):260. doi: 10.1007/s12032-015-0706-8. Epub 2015 Oct 31.
Ovarian cancer is the most lethal malignancy in female patients, and chemoresistance is the major contribution to low over survival rate. We aim to investigate the correction between Sirt1 expression and chemoresistance in serous epithelial ovarian cancer (EOC) and prognosis significance of Sirt1. Immunochemistry was used to determine the location pattern and expression of Sirt1 in a total of 63 serous EOC patients (28 cases of chemoresistance patients and 35 chemosensitive).The relationship between Sirt1 expression and clinicopathological features of serous EOC was analyzed. Univariate analysis and multifactor logistic regression analysis were applied to investigate risk factor for chemoresistance. Cox proportional hazards regression model and Kaplan-Meier survival analysis were applied to determine the prognosis factor and survival time. Immunohistochemistry proved that over-expression of nuclear Sirt1 was related to chemoresistance (P = 0.039). Multivariate logistic regression analysis proved that the nuclear expression of Sirt1 (P = 0.018) and the lymph node metastasis (P = 0.037) was independent risk factors for chemoresistance in serous epithelial ovarian cancer. Multivariate Cox regression result indicated that expression of Sirt1 (P = 0.026, RR 2.434, 95 % CI 1.109-5.339) and stage (P = 0.005, RR 2.366, 95 % CI 1.288-4.345) was independent prognostic factors. Kaplan-Meier analysis showed that the survival rate is significantly decreased in the Sirt1 highly expressed group. Western blot result showed that the protein level of Sirt1 was significantly higher in chemoresistant group compared with in sensitive group. In conclusion, our results proved that over-expression of Sirt1 could play an important role in chemoresistance of serous EOC and could be a prognosis indicator for the patient's survival outcome.
卵巢癌是女性患者中最致命的恶性肿瘤，化疗耐药是导致生存率低下的主要原因。我们旨在研究沉默调节蛋白1（Sirt1）表达与浆液性上皮性卵巢癌（EOC）化疗耐药之间的相关性以及Sirt1的预后意义。采用免疫化学方法确定63例浆液性EOC患者（28例化疗耐药患者和35例化疗敏感患者）中Sirt1的定位模式和表达情况。分析Sirt1表达与浆液性EOC临床病理特征之间的关系。采用单因素分析和多因素逻辑回归分析研究化疗耐药的危险因素。应用Cox比例风险回归模型和Kaplan-Meier生存分析确定预后因素和生存时间。免疫组织化学证明，细胞核Sirt1的过表达与化疗耐药相关（P = 0.039）。多因素逻辑回归分析证明，Sirt1的细胞核表达（P = 0.018）和淋巴结转移（P = 0.037）是浆液性上皮性卵巢癌化疗耐药的独立危险因素。多因素Cox回归结果表明，Sirt1的表达（P = 0.026，RR 2.434，95%CI 1.109 - 5.339）和分期（P = 0.005，RR 2.366，95%CI 1.288 - 4.345）是独立的预后因素。Kaplan-Meier分析表明，Sirt1高表达组的生存率显著降低。蛋白质印迹结果表明，化疗耐药组中Sirt1的蛋白水平明显高于敏感组。总之，我们的结果证明，Sirt1的过表达在浆液性EOC的化疗耐药中可能起重要作用，并且可能是患者生存结果的预后指标。
