几项生物学指标与肺癌患者5年生存率的相关性分析

Correlation between several biological parameters and 5-year survival rate in patients with lung cancer

目的:评估p53蛋白、p21,CD44v,P-糖蛋白及常用临床病理指标对判断肺癌患者预后的意义。方法:收集北京协和医院胸外科1998-02/07收治的肺癌患者30例,所有患者在术前均未接受过化疗或放疗。采用流式细胞术检测30例冻存的肺癌及10例相应远离肿瘤部位的正常肺组织中p21,CD44v,P-糖蛋白、p53蛋白的表达,结合临床病理指标,与患者术后5年生存率及生存期进行单因素和多因素分析。计数资料采用精确概率法进行检验,同时用Cox比例风险模型对患者的预后进行多因素分析。结果:①肺癌组织中p53蛋白、p21,CD44v,P-糖蛋白的阳性率明显高于远癌肺组织(P<0.01)。②p53蛋白、CD44v,P-糖蛋白阳性表达者5年生存率显著低于阴性表达者(P<0.05)。吸烟患者5年生存率亦明显低于不吸烟的患者(12%比62%,P<0.05)。随着病理分期的增加、肿瘤直径的增大和分化程度的降低,患者5年生存率亦呈下降趋势(P<0.01或0.05)。③单因素分析表明,影响患者术后5年生存率的因素为p53蛋白、CD44v、P-糖蛋白的异常表达、患者是否吸烟及手术时p-TNM分期、肿瘤大小和分化程度(P<0.05或0.01)。④多因素分析则显示,仅p53的异常表达、患者是否吸烟及p-TNM分期是影响患者术后生存期的独立预后指标。结论:p53蛋白、CD44v、P-糖蛋白的异常表达、患者是否吸烟、p-TNM分期、肿瘤大小及分化程度对肺癌预后有重要意义,其中p53蛋白的异常表达、患者是否吸烟和p-TNM分期可能是更有价值的预后指标。

AIM： To evaluate the prognostic value of several molecular markers （p53 protein, p21, CD44v and P-glycosidoprotein （P-gp） aswellasgeneralclinical pathological parameters on judgment of the prognosis in patients with lung cancer. METHODS： A total of 30 patients with lung cancer were collected from the Department of Thoracic Surgery in Peking Union Medical College Hospital between February and July 1998. None of subjects received preoperative chemotherapy or radiotherapy. The flow cytometry was used to detect 30 frozen lung cancer specimens and the expressions of p21, CD44v, P-gp and p53 protein in normal lung tissues that far away from the cancer in 10 patients. Combining with clinical pathological parameters, the survival rate and life span of patients at 5 years after operation were analyzed with univariate analysis and multiplicity. The numeration data were inspected with exact probability, meanwhile, Cox proportional hazard model was adopted for prognostic multiplicity in patients. RESULTS： （1） In lung cancer, the positive expression rates of four molecular markers in cancer tissues were much higher than those in non-cancer tissues （P 〈 0.01）. （2）The 5-year survival rate of patients who were positive in expressions of p53 protein, CD44v and P-GP was significantly lower than that of negative patients （12% vs. 62%, P 〈 0.05）. As the increase of pathological stages, enlargement of diameter in cancer and decrease of differentiation, the 5-year survival rate was also in a downtrend （P 〈 0.01 or 0.05）. （3）Univariate analysis manifested that the prognostic factors that influenced 5-year overall survival rate were the abnormal expressions of CD44v, P-GP and p53 protein, smoking, p-TNM stage, tumor size and histological differentiation at the time of operation （P 〈 0.05 or 0.01）. （4）Multivariate analysis demonstrated that the abnormal expression of p53 protein, smoking and p-TNM stage were significant independent prognostic factors for survival. CONCLUSION： Although the abnormal expressions of CD44v, P-GP and p53 protein, smoking, p-TNM stage, tumor size and histological differentiation are indicators of poor prognosis in diagnosing lung cancer, the abnormal expression of p53 protein, smoking and p-TNM stage may be the more important prognostic factors.