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The association between copper transporters and the prognosis of cancer patients undergoing chemotherapy: a meta-analysis of literatures and datasets
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Abstract
Si Sun1,*, Jing Cai1,*, Qiang Yang1, Simei Zhao1 and Zehua Wang1
1 Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China
* These authors have contributed equally to this study
Correspondence to:
Zehua Wang, email:
Keywords: CTR1, ovarian cancer, lung cancer, platinum-based chemotherapy, meta-analysis
Received: June 30, 2016 Accepted: December 01, 2016 Published: December 12, 2016
Abstract
Copper transporter 1 (CTR1), copper transporter 2 (CTR2), copper-transporting p-type adenosine triphosphatase 1 and 2 (ATP7A and ATP7B) are key mediators of cellular cisplatin, carboplatin and oxaliplatin accumulation. In this meta-analysis, we aimed to evaluate the relation of CTR1, CTR2, ATP7A and ATP7B to overall survival (OS), progression-free survival (PFS), disease-free survival (DFS) and treatment response (TR) of cancer patients who received chemotherapy based on published literatures, the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) datasets. Hazard ratios (HRs) and odds ratios (ORs) were pooled using random-effect models. Subgroup analysis and sensitivity analysis were conducted; heterogeneity and publication bias were assessed. Twelve literatures and eight datasets with 2149 patients were included. Our results suggested that high CTR1 expression was associated with favorable OS, PFS, DFS and TR in cancer patients who underwent chemotherapy with acceptable heterogeneity. The relationship of CTR1 to cancer prognosis remained significant in the subgroup of patients who underwent platinum-based chemotherapy, the patients with ovarian cancer and those with lung cancer. The significance of these relationships was not influenced by geological region of publication, data origin or detection method. However, there was no evidence for relation of CTR2, ATP7A or ATP7B to OS, PFS, DFS or TR. Test of publication bias and sensitivity analysis suggested a robustness of all the summary effect estimates. In conclusion, high CTR1 level predicts prolonged survival and enhanced response to chemotherapy in cancer patients who underwent chemotherapy and CTR1 might be a potential target to circumvent chemotherapy resistance.
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