Abstract:
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.