非小细胞肺癌患者病理组织中MTH1的表达及临床意义研究

Expression and clinical significance of MTH1 in pathological tissues of patients with non-small cell lung cancer

目的探索氧化嘌呤核苷三磷酸酶mutT同系物1(MTH1)在非小细胞肺癌(NSCLC)组织中的表达及其临床意义。方法收集2011年3月至2013年3月在安徽医科大学附属省立医院手术治疗的诊断为NSCLC的197例患者的病理组织,使用免疫组织化学方法检测MTH1蛋白的表达,并将患者分为MTH1高表达和低表达两组,分析MTH1表达与患者临床特征之间的关系,采用Kaplan-Meier生存曲线法分析MTH1表达强度与患者预后的关系,Cox比例风险模型分析MTH1表达对患者总生存率和无瘤生存率的影响。结果MTH1高表达患者111例(56.3%),低表达86例(43.7%)。MTH1高表达和男性、吸烟大于20包/年、鳞癌、病理分期大于Ⅰ期、肿瘤直径大于3cm、淋巴结转移、胸膜浸润阳性、淋巴管浸润和血管浸润呈显著性相关(P<0.05)。MTH1高表达组和MTH1低表达组5年总生存率分别为81.6%和92.3%(P=0.0011),5年无瘤生存率分别为55.0%和83.7%(P=0.0002)。MTH1表达(HR=1.713,95%CI:1.865~4.118,P=0.0470)和淋巴结转移(HR=9.190,95%CI:2.824~39.457,P<0.01)是患者总生存率的独立危险因素;MTH1表达(HR=1.605,95%CI:1.627~3.248,P=0.0390)和淋巴结转移(HR=4.502,95%CI:1.942~11.546,P=0.0003)是患者无瘤生存率的独立危险因素。结论 MTH1可作为NSCLC预后评价的独立影响因素,MTH1高表达NSCLC患者表现出更多恶性临床特征。

Objective To investigate the expression and clinical significance of osmium nucleoside triphosphatase mutT homolog 1 (MTH1) in non-small cell lung cancer (NSCLC) tissues. Methods The pathological tissue samples of 197 NSCLC patients from March 2011 to March 2013 were collected.Immuno-histochemical method was used to evaluate the expression of MTH1 protein,then the patients were divided into the high-expressed group and the low-expressed group according to the level of MTH1.The relationship between MTH1 expression and clinical characteristics of patients was analyzed.Kaplan-Meier survival curve method was used to analyze the expression of MTH1 and prognosis of patients.Cox proportional hazards model was used to analyze the MTH1′s impact on overall survival and disease-free survival of the patients. Results MTH1 was highly expressed in 111 cases (56.3%) and lowly expressed in 86 cases (43.7%).High expression of MTH1 was positive associated with male,smoking>20 packs/years,squamous cell carcinoma,pathological stage>stage Ⅰ,tumor diameter>3 cm,lymph node metastasis,pleural infiltration positive,lymph node infiltration and vascular infiltration significantly.The 5-year overall survival rates and 5-year disease-free survival rates in the high- or low- expressed groups were 81.6% vs. 92.3%( P =0.001 1),and 55.0% vs. 83.7%( P = 0.000 2).MTH1 expression ( HR =1.713,95% CI :1.865-4.118, P =0.047 0) and lymph node metastasis ( HR =9.190,95% CI :2.824-39.457, P <0.01) were independent risk factors for overall survival;MTH1 expression ( HR =1.605,95% CI :1.627-3.248, P =0.039 0) and lymph node metastasis ( HR = 4.502 ,95% CI :1.942-11.546, P =0.000 3) were independent risk factors for disease-free survival. Conclusion MTH1 can be used as an independent factor in the prognosis evaluation of NSCLC,and NSCLC patients with high-expressedMTH1 show more malignant clinical features.