SIRT2在宫颈癌组织中的表达及其临床意义

  目的  研究沉默信息调节因子2 (silencing information regulatory 2，SIRT2)在宫颈癌组织、宫颈上皮内瘤变(cervical intraepithelial neoplasia，CIN)组织的表达及临床意义。  方法  免疫组织化学法(immunohistochemistry，IHC)检测262例宫颈癌组织、75例CIN组织及75例正常宫颈组织石蜡标本中SIRT2蛋白的表达，并分析SIRT2蛋白表达与宫颈癌临床病理特征的关系；采用Western blot法验证40例宫颈癌和40例正常宫颈新鲜组织标本中SIRT2蛋白的表达差异；采用短发夹RNA(short hairpin RNA，shRNA)-SIRT2沉默SIRT2在HeLa细胞中的表达，通过MTT、划痕实验检测下调SIRT2表达对HeLa细胞增殖、迁移能力的影响。  结果  ① IHC结果显示，正常宫颈、CIN、宫颈癌组织中SIRT2蛋白的表达逐渐升高(P＜0.001)。Western blot也证实SIRT2蛋白的表达在宫颈癌组织较正常宫颈组织中高(P＜0.001)；② SIRT2在宫颈癌组织中高表达与宫颈癌的病理类型(腺癌)、FIGO分期高、有淋巴结转移及有高危HPV感染有关(P均＜0.05)，SIRT2表达水平与年龄、肿瘤分化程度、有无盆腔转移、有无累及宫颈间质及深度、有无累及颈体交界及阴道断端等无关(P均＞0.05)，宫颈癌SIRT2蛋白高表达组患者的死亡率高于SIRT2蛋白低表达组(P＜0.05)；③ shRNA-SIRT2能抑制HeLa细胞中SIRT2蛋白的表达(P＜0.05)，且下调SIRT2蛋白表达后，HeLa细胞的增殖和迁移能力减弱(P＜0.05)。  结论  SIRT2在宫颈癌变过程中可能有促进作用，SIRT2可能与宫颈癌的恶性程度发展有关。

Expression Level of SIRT2 in Cervical Cancer Tissue and Its Clinical Significance

  Objective   To investigate the expression level of silencing information regulatory 2 (SIRT2) in cervical cancer and CIN tissues and its clinical significance.  Methods   Immunohistochemistry was carried out to examine the expression of SIRT2 in 262 cases of cervical cancer tissues, 75 cases of precancerous lesions and 75 cases of normal cervical tissues, and the clinical implications of SIRT2 was further analyzed. The protein expression level of SIRT2 in 40 cervical cancer fresh tissue samples and 20 normal cervical tissue samples was detected by Western blot. shRNA-SIRT2 virus was transfected into HeLa cells to obtain the SIRT2-down-regulated HeLa cells. And the influence of down-regulation of SIRT2 on cell proliferation and migration was investigated by MTT and Scratch test.  Results   Immunohistochemical results showed that SIRT2 protein expression level gradually increased in cervical cancer, CIN and normal cervix tissues (P < 0.001). Western blot confirmed that SIRT2 expression level was higher in cervical cancer tissues than in normal cervix tissues (P < 0.001). The expression level of SIRT2 in cervical cancer was correlated with some factors, such as lymph node metastasis, histological type, clinical staging and HPV infection (P < 0.05). At the same time, it was independent of some factors including age, differentiation degree, pelvic metastasis, whether involving the cervical interstitial and the involvement depth and whether involving the neck junction and vaginal ends (P>0.05). Mortality in SIRT2 high expression patient group was higher than that of SIRT2 low expression patient group (P < 0.05). shRNA interference technique could effectively inhibit the expression level of SIRT2 in HeLa cells (P < 0.05). MTT assay and Scratch test indicated that down-regulation of SIRT2 expression inhibited the proliferation and migration of HeLa cells (P < 0.05).  Conclusion   SIRT2 may play a promoting role in the progress of cervical cancer, and SIRT2 may be related to the development of malignant degree of cervical cancer, and the inhibition of SIRT2 expression may be a potential therapeutic target for cervical cancer.