title: Expression of the copper transporters hCtr1, ATP7A and ATP7B is associated with the response to chemotherapy and survival time in patients with resected non-small cell lung cancer.
abstract: Copper transporter family proteins may regulate the chemoresistance of non-small cell lung cancer (NSCLC) to platinum-based anticancer drugs. The present study aimed to investigate the expression of these proteins in lung cancer tissue specimens for association with clinicopathological data and patient responses to chemotherapy and survival. A total of 54 patients with surgically resected NSCLC that received first-line platinum-based doublet chemotherapy were recruited in the present study, and the paraffin-embedded pre-treatment tumor tissue specimens were subjected to immunohistochemical analysis for the expression of human copper transporter 1 (hCtr1) and copper-transporting p-type adenosine triphosphatase 1 (ATP7A) and 2 (ATP7B). This cohort of patients with NSCLC received platinum-based chemotherapy subsequent to the surgical removal of tumor lesions. ATP7B expression was found to be significantly associated with tumor cell differentiation, while hCtr1 expression was significantly associated with improved chemotherapeutic responses. The median survival time was 20 months in patients possessing tumors with high ATP7A expression, but >66 months in patients possessing tumors with low ATP7A expression at the end of the follow-up (P<0.001). The median survival time at the end of the follow-up was 15 months in patients with low tumor hCtr1 expression, but >66 months in patients with high tumor hCtr1 expression (P<0.001). High hCtr1 and low ATP7A expression were each favorable prognostic factors subsequent to chemotherapy for patients with resected NSCLC. Multivariate analysis revealed that high hCtr1 expression combined with low ATP7A expression, good tumor differentiation and female gender were all favorable independent predictive and prognostic factors for patients with resected NSCLC following chemotherapy. High hCtr1 expression combined with low ATP7A expression was associated with an improved prognosis in patients with resected NSCLC that received platinum-based chemotherapy. Surgery combined with neoadjuvant chemotherapy may improve the survival time of patients with NSCLC.
authors.affiliation: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Tian
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Mingwei
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Tianjun
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Asmitananda
authors.initials: A
authors.lastname: Thakur
keywords: NSCLC; copper transporters; platinum