Yang Tian, Chen Mingwei, Chen Tianjun, Thakur Asmitananda
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.
Oncol Lett. 2015 Oct;10(4):2584-2590. doi: 10.3892/ol.2015.3531. Epub 2015 Jul 24.
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.
铜转运蛋白家族蛋白可能调节非小细胞肺癌（NSCLC）对铂类抗癌药物的化疗耐药性。本研究旨在调查这些蛋白在肺癌组织标本中的表达情况，及其与临床病理数据、患者化疗反应和生存率的相关性。本研究共纳入54例接受一线铂类双药化疗且手术切除的NSCLC患者，对石蜡包埋的治疗前肿瘤组织标本进行免疫组织化学分析，检测人铜转运蛋白1（hCtr1）、铜转运P型三磷酸腺苷酶1（ATP7A）和2（ATP7B）的表达。该队列NSCLC患者在手术切除肿瘤病灶后接受铂类化疗。结果发现，ATP7B表达与肿瘤细胞分化显著相关，而hCtr1表达与化疗反应改善显著相关。随访结束时，ATP7A高表达肿瘤患者的中位生存时间为20个月，而ATP7A低表达肿瘤患者的中位生存时间>66个月（P<0.001）。随访结束时，肿瘤hCtr1低表达患者的中位生存时间为15个月，而肿瘤hCtr1高表达患者的中位生存时间>66个月（P<0.001）。高hCtr1和低ATP7A表达均为NSCLC切除术后患者化疗后的良好预后因素。多因素分析显示，高hCtr1表达联合低ATP7A表达、良好的肿瘤分化和女性性别均为NSCLC切除术后患者化疗后的良好独立预测和预后因素。高hCtr1表达联合低ATP7A表达与接受铂类化疗的NSCLC切除术后患者的预后改善相关。手术联合新辅助化疗可能改善NSCLC患者的生存时间。
