凋亡抑制蛋白Survivin在人非小细胞肺癌中的表达及其与COX-2蛋白表达和细胞凋亡的关系

Expression of Survivin in Non-small Cell Lung Carcinoma of Human and Its Association with COX-2 and Apoptosis

目的探讨Survivin蛋白和COX2蛋白在人非小细胞肺癌(NSCLC)组织中的表达情况及与细胞凋亡水平的关系,并探讨与预后的关系。方法对75例非小细胞肺癌石蜡组织切片、30例正常肺组织,使用免疫组织化学SP法检测Survivin和COX2的表达,用TUNEL法原位测定细胞凋亡水平。结果非小细胞肺癌组织中Survivin和COX2的阳性率分别为70.6%和68.0%,均显著高于正常肺组织中的阳性率6.7%和10.0%(P均<0.05)。Survivin表达与COX2表达呈正相关(r=0.78,P<0.05),Survivin与凋亡指数呈负相关(r=0.86,P<0.05),COX2与凋亡指数呈负相关(r=0.75,P<0.05)。Survivin阴性组的AI高于Survivin阳性组(z=5.10,P<0.0001)。生存分析显示Survivin阳性组的5年生存率明显低于Survivin阴性组。结论Survivin与COX2在NSCLC中表达升高,在NSCLC的发生发展中起了重要作用,并与NSCLC的恶性行为相关,Survivin对于监测预后有重要意义。同时Survivin可能成为治疗NSCLC的靶点。

Objective To investigate the expression of survivin and cyclooxygenase-2 (COX-2) in non-small cell lung cancer (NSCLC) of human and to explore the relationship with apoptosis as well as prognosis. Methods By immunohistochemical S-P assay, the expression of survivin and COX-2 protein were examined in 75 paraffin sections of tissue from NSCLC and 30 from normal pulmonary tissue. The level of apoptosis was evaluated by TUNEL in situ. Results The two positive expression rates were significantly higher in NSCLC than that in normal pulmonary tissue (70.6%, 68.0% vs 6.7%, 10.0%, both p<0.05). Survivin expression was positively related to COX-2 expression (p<0.05). Expression of both survinin and COX-2 were negatively related to apoptosis index (AI) (both p<0.05). AI was remarkably lower in survivin-positive than that in survivin-negative (p<0.05), so was five-year survival rate by survival analysis. Conclusion Expression of both survivin and COX-2 increases in NSCLC, which may associate with the malignancy, could play an important role in the carcinogenesis and progression of NSCLC. Up-regulation of expression of survivin predicts poorer prognosis. Survivin might become a new target for treatment of NSCLC.