ATP7A在非小细胞肺癌中的表达及其临床意义

Expression and Clinical Significance of ATP7A in Non-small Cell Lung Cancer

目的:探讨晚期非小细胞肺癌(NSCLC)组织中P型铜转运ATP酶(ATP7A)的表达与患者临床病理特征及预后的关系。方法:采用免疫组织化学法检测89例未接受手术及放疗而只接受含顺铂方案一线化疗的晚期非小细胞肺癌组织中ATP7A的表达情况,并分析ATP7A表达与患者临床病理特征及预后的关系。结果:ATP7A的免疫阳性反应主要定位于非小细胞肺癌细胞的细胞质,ATP7A的标本阳性率为41.6%(37/89),而在间质及正常肺组织均未见表达;ATP7A表达状态与含顺铂方案的化疗反应及组织分化分级呈正相关(P=0.001,P=0.039),而与年龄(P=0.469)、性别(P=0.442)、分期(P=0.436)、PS(P=0.361)、组织学分型(P=0.670)及CEA水平(P=0.661)无关;Kaplan-Meier法生存分析显示ATP7A阳性表达的患者总生存(OS)低于ATP7A阴性表达患者(P=0.021);单因素分析显示ATP7A、分期、PS、CEA水平和组织分化分级和OS呈正相关(P值=0.021、P=0.019、P=0.004、P=0.022、P=0.010);多因素分析显示ATP7A、分期、CEA水平和组织分化分级是接受含铂方案化疗的晚期非小细胞肺癌患者OS的独立预后因子(P=0.045、P=0.001、P=0.003、P=0.009)。结论:ATP7A在大部分晚期非小细胞肺癌组织中均有表达,ATP7A表达水平与晚期非小细胞肺癌的组织分化分级、含铂方案化疗疗效及患者生存期密切相关,提示ATP7A与非小细胞肺癌的发生发展有关。

Objective： To investigate the expression of P-type copper transporting adenosine triphosphatase ATP7A in patients with advanced non-small cell lung cancer （NSCLC） and to analyze its correlation with the clinicopathologic features and prognosis of advanced NSCLC patients. Methods： In the specimens of 89 advanced NSCLC patients treated with first line cisplatin based chemotherapy only （no surgery or radiotherapy）, the expression of ATP7A protein was determined with immunohistochemistry. The correlation among the ATP7A expression, clinicopathologic features and prognosis of the patients was analyzed with SPSS 16.0 statistical software package. Results： The positive immune reaction of ATP7A was mainly observed in cytoplasmic staining of NSCLC cells and was detected in 41.6% （ 37/89 ） cases. However, the expression of ATP7A wasn＇t found in adjacent mesenchymal tissue of the tumor or normal lung tissue. The ATP7A expression was related to the response to cisplatin-based chemotherapy and histological grade （ P = 0.001 and 0.039, respectively）. There was no significant correlation between the ATP7A expression and the following factors： age （ P = 0.469 ）, sex （ P = 0.442 ）, staging （P = 0.436）, PS （ P = 0.361 ）, histological subtype （ P = 0.67 ） or serum CEA status （ P = 0.661 ）. Kaplan-Meier analysis indicated that advanced NSCLC patients with ATP7A positive expression showed a lower overall survival （OS） compared to the same patients with ATP7A negative expression （ log-rank test, P = 0.021）. Univariate analysis demonstrated that ATP7A, clinical staging, PS, CEA status and histological grading were significantly correlated with OS （ P = 0.021, 0.019, 0.004, 0.022 and 0.013, respectively）. And multivariate analysis showed that ATP7A, clinical staging, CEA status and histological grading were the independent factors of these NSCLC patients treated with the cisplatin-based chemotherapy （ P = 0.045, 0.001, 0.003 and 0.009, respectively）. Conclusion： ATP7A is positively expressed in most of the advanced NSCLC tissue. The expression level of ATP7A is an important factor affecting the histological grading of the tumor tissue, the response to platinum-based chemotherapy and the prognosis of advanced NSCLC patients. These factors indicate that ATP7A might be involved in the genesis and development of NSCLC and could be a resistant marker for platinum-based chemotherapy and a prognostic factor for survival in NSCLC patients treated with platinum-based chemotherapy.