Beclin1、p53与肺癌恶性度及疗效预后的相关性研究

The correlation between Beclin1,p53 and the malignancy,efficacy and prognosis of lung cancer

目的通过定量检测肺组织中Beclin1和p53表达水平,分析自噬蛋白Beclin1与凋亡蛋白P53在肺癌发生发展中的作用,研究二者之间及其与肺癌临床病理分期的关系、为肺癌早期诊断提供新的思路和实验依据。方法选取外科手术或纤维支气管镜肺组织56例,依据2003年UICC公布的肺癌TNM分期标准同时结合临床表现、胸部CT、X线检查、纤维支气管镜检查、腹部CT或B超等将入选的50例病例进行分组:其中Ⅰ期5例,Ⅱ期10例,Ⅲ期(ⅢA+ⅢB)26例,Ⅳ期9例,各组年龄、性别等控制情况基本匹配。组织病理学分级按2003年UICC标准:G17例,G219例,G324例。另取6例癌旁组织或者病理确诊为正常组织作为对照组织。采用流式细胞术检测和分析不同病理分期以及不同临床分期肺癌组织中Beclin1、p53的表达水平,对该表达情况与对应的分期进行样本均数两两对比式统计学分析,并与正常肺组织作对照。结果 P53蛋白阳性表达百分率:肿瘤患者(63.96±9.43)%显著高于正常对照组(24.90±4.68)%,t=49.46,P<0.05;肿瘤转移者显著高于未转移者,P<0.05;并且P53蛋白表达随患者临床分期和病理分级的增加而逐渐增高(P<0.05)。Beclin1蛋白检出率的变化规律与P53蛋白检出率的变化相反:肿瘤患者Beclin1蛋白(31.72±20.53)%,显著低于正常对照组(92.26±4.51)%,t=35.84,P<0.05;该指标随患者临床分期和病理分级的增加而逐渐降低(P<0.05)。Beclin1蛋白与P53蛋白二者相关性分析,Beclin1与p53的表达呈负相关,r=-0.848,P<0.05。结论 Beclin1与p53的联合检测可以作为肺癌诊断指标,为估计肺癌的恶性度及预后提供依据。Beclin1与P53蛋白表达水平与肺癌发生发展的关系密切,肿瘤发生过程中细胞自噬作用降低和抗凋亡作用增强同时并存,提高自噬能力成为肿瘤治疗的又一途径。

Objective To analyze the roles of autophagy protein Beclin1 and apoptotic protein p53 in the occurrence and development of lung cancer,study their relationship with each other and with the pathological stages,so as to provide new ideas and experimental evidence for early diagnosis of lung cancer.Method According to TNM staging criteria of lung cancer published in 2003 by UICC,combined with clinical manifestations,chest CT,X-ray examination,bronchoscopy,abdominal CT or type B ultrasonic,50 cases of lung tissue from surgery or fiberoptic bronchoscope were grouped,including 5 cases of stage I,10 cases of stage Ⅱ,26 cases of stage III（IIIA＋IIIB）,9 cases of stage IV.The age,gender and other conditions in each group were evenly matched.The histopathological classification according to UICC criteria 2003 was as follows： 7 cases of G1,19 cases of G2 and 24 cases of G3.The other six cases of cancer tissues obtained or diagnosed as normal tissue were used as the control.Flow cytometry was used to detect and analyze the expressions of Beclin1 and p53 in lung cancer tissues in different pathological stages and different clinical stages.Result The expression rate of p53 protein in lung cancer patients was（63.96±9.43）%,significantly higher than the（24.90±4.68）% of normal control group（t=49.46,P0.05）;It was significantly higher in the patients with tumor metastasis than in those without metastasis（P0.05）;and p53 protein expression gradually increased with clinical stage and the increase of pathological grade（P0.05）.The detection rate of Beclin1 protein in cancer patients was（31.72±20.53）%,significantly lower than the（92.26±4.51）% of control group（t=35.84,P0.05）;The index gradually reduced with the clinical stage and the increase of pathological grade（P0.05）.The expressions of Beclin1 and p53 were negatively correlated（r=-0.848,P0.05）.Conclusion The combined detection of Beclin1 and p53 can be used as indicators to lung cancer and provide the basis for prognosis of malignancy and efficacy of lung cancer.The expression levels of Beclin1 and p53 protein are closely related to the development of lung cancer.Reduced lautophagy and enhanced anti-apoptosis coexist in the process of tumor formation,thus,raising the macrophages＇ ability may become another alternative for cancer therapy.