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The ATP7B genetic polymorphisms predict clinical outcome to platinum-based chemotherapy in lung cancer patients

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Tumor Biology

Abstract

This study aims to investigate the influence of ATP7B genetic polymorphism to platinum-based chemotherapy in Chinese Han lung cancer patients. A total of 338 Chinese Han lung cancer patients were enrolled in this study. All patients underwent at least two cycles of platinum-based chemotherapy. Four tag SNPs of ATP7B (rs1061472, rs9535826, rs7999812, and rs9535828) were selected to evaluate their impacts to platinum-based chemotherapy in these patients. ATP7B rs9535828 and rs9535826 were found to be associated with platinum resistance in Chinese Han lung cancer patients. Patients with A allele in ATP7B rs9535828 presented an increased susceptibility to platinum drugs (OR 1.96, 95 % CI 1.17–3.30, p < 0.01). Patients with G allele in ATP7B rs9535826 had the highest susceptibility to platinum drugs (OR 2.05, 95 % CI 1.19–3.52, p < 0.01). Our findings suggest that ATP7B genetic polymorphisms could affect the therapeutic efficacy of platinum-based chemotherapy, and ATP7B gene might be considered as predictive markers for the efficacy evaluation of platinum-based chemotherapy in Chinese Han lung cancer patients.

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References

  1. Wheate NJ, Walker S, Craig GE, Oun R. The status of platinum anticancer drugs in the clinic and in clinical trials. Dalton Trans. 2010;39:8113–27.

    Article  CAS  PubMed  Google Scholar 

  2. Stordal B, Davey M. Understanding cisplatin resistance using cellular models. IUBMB life. 2007;59:696–9.

    Article  CAS  PubMed  Google Scholar 

  3. Kelland L. The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer. 2007;7:573–84.

    Article  CAS  PubMed  Google Scholar 

  4. Shahzad MM, Lopez-Berestein G, Sood AK. Novel strategies for reversing platinum resistance. Drug Resist Updat: Rev Commentaries Antimicrob Anticancer Chemother. 2009;12:148–52.

    Article  CAS  Google Scholar 

  5. La Fontaine S, Mercer JF. Trafficking of the copper-atpases, atp7a and atp7b: Role in copper homeostasis. Arch Biochem Biophys. 2007;463:149–67.

    Article  PubMed  Google Scholar 

  6. Komatsu M, Sumizawa T, Mutoh M, Chen ZS, Terada K, Furukawa T, et al. Copper-transporting p-type adenosine triphosphatase (atp7b) is associated with cisplatin resistance. Cancer Res. 2000;60:1312–6.

    CAS  PubMed  Google Scholar 

  7. Terada K, Schilsky ML, Miura N, Sugiyama T. Atp7b (wnd) protein. Int J Biochem Cell Biol. 1998;30:1063–7.

    Article  CAS  PubMed  Google Scholar 

  8. Harris ED, Qian Y, Tiffany-Castiglioni E, Lacy AR, Reddy MC. Functional analysis of copper homeostasis in cell culture models: a new perspective on internal copper transport. Am J Clin Nutr. 1998;67:988S–95.

    CAS  PubMed  Google Scholar 

  9. Kuo MT, Chen HH, Song IS, Savaraj N, Ishikawa T. The roles of copper transporters in cisplatin resistance. Cancer Metastasis Rev. 2007;26:71–83.

    Article  CAS  PubMed  Google Scholar 

  10. Safaei R. Role of copper transporters in the uptake and efflux of platinum containing drugs. Cancer Lett. 2006;234:34–9.

    Article  CAS  PubMed  Google Scholar 

  11. Katano K, Safaei R, Samimi G, Holzer A, Rochdi M, Howell SB. The copper export pump atp7b modulates the cellular pharmacology of carboplatin in ovarian carcinoma cells. Mol Pharmacol. 2003;64:466–73.

    Article  CAS  PubMed  Google Scholar 

  12. Samimi G, Katano K, Holzer AK, Safaei R, Howell SB. Modulation of the cellular pharmacology of cisplatin and its analogs by the copper exporters atp7a and atp7b. Mol Pharmacol. 2004;66:25–32.

    Article  CAS  PubMed  Google Scholar 

  13. Nakayama K, Kanzaki A, Terada K, Mutoh M, Ogawa K, Sugiyama T, et al. Prognostic value of the cu-transporting atpase in ovarian carcinoma patients receiving cisplatin-based chemotherapy. Clin Cancer Res: Off J Am Assoc Cancer Res. 2004;10:2804–11.

    Article  CAS  Google Scholar 

  14. Aida T, Takebayashi Y, Shimizu T, Okamura C, Higasimoto M, Kanzaki A, et al. Expression of copper-transporting p-type adenosine triphosphatase (atp7b) as a prognostic factor in human endometrial carcinoma. Gynecol Oncol. 2005;97:41–5.

    Article  CAS  PubMed  Google Scholar 

  15. Leslie EM, Letourneau IJ, Deeley RG, Cole SP. Functional and structural consequences of cysteine substitutions in the nh2 proximal region of the human multidrug resistance protein 1 (mrp1/abcc1). Biochemistry. 2003;42:5214–24.

    Article  CAS  PubMed  Google Scholar 

  16. Yin JY, Huang Q, Yang Y, Zhang JT, Zhong MZ, Zhou HH, et al. Characterization and analyses of multidrug resistance-associated protein 1 (mrp1/abcc1) polymorphisms in Chinese population. Pharmacogenet Genomics. 2009;19:206–16.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Pasanen MK, Neuvonen PJ, Niemi M. Global analysis of genetic variation in slco1b1. Pharmacogenomics. 2008;9:19–33.

    Article  CAS  PubMed  Google Scholar 

  18. Xu X, Ren H, Zhou B, Zhao Y, Yuan R, Ma R, et al. Prediction of copper transport protein 1 (ctr1) genotype on severe cisplatin induced toxicity in non-small cell lung cancer (nsclc) patients. Lung Cancer (Amsterdam, Netherlands). 2012;77:438–42.

    Article  Google Scholar 

  19. Xu X, Duan L, Zhou B, Ma R, Zhou H, Liu Z. Genetic polymorphism of copper transporter protein 1 is related to platinum resistance in Chinese non-small cell lung carcinoma patients. Clin Exp Pharmacol Physiol. 2012;39:786–92.

    Article  CAS  PubMed  Google Scholar 

  20. Fukushima-Uesaka H, Saito Y, Maekawa K, Kurose K, Sugiyama E, Katori N, et al. Genetic polymorphisms of copper- and platinum drug-efflux transporters atp7a and atp7b in Japanese cancer patients. Drug Metab Pharmacokinet. 2009;24:565–74.

    Article  CAS  PubMed  Google Scholar 

  21. Panichareon B, Taweechue K, Thongnoppakhun W, Aksornworanart M, Pithukpakorn M, Yenchitsomanus PT, et al. Six novel atp7b mutations in Thai patients with Wilson disease. Eur J Med Gen. 2011;54:103–7.

    Article  Google Scholar 

  22. Ettinger D, Johnson B. Update: Nccn small cell and non-small cell lung cancer clinical practice guidelines. J Natl Compr Cancer Netw: JNCCN. 2005;3 Suppl 1:S17–21.

    PubMed  Google Scholar 

  23. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16.

    Article  CAS  PubMed  Google Scholar 

  24. Barrett JC: Haploview: Visualization and analysis of snp genotype data. Cold Spring Harbor protocols 2009;2009:pdb ip71

  25. Jurinke C, Oeth P, van den Boom D. Maldi-tof mass spectrometry: A versatile tool for high-performance DNA analysis. Mol Biotechnol. 2004;26:147–64.

    Article  CAS  PubMed  Google Scholar 

  26. Lutsenko S, Barnes NL, Bartee MY, Dmitriev OY. Function and regulation of human copper-transporting atpases. Physiol Rev. 2007;87:1011–46.

    Article  CAS  PubMed  Google Scholar 

  27. Safaei R, Adams PL, Maktabi MH, Mathews RA, Howell SB. The cxxc motifs in the metal binding domains are required for atp7b to mediate resistance to cisplatin. J Inorg Biochem. 2012;110:8–17.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Dolgova NV, Olson D, Lutsenko S, Dmitriev OY. The soluble metal-binding domain of the copper transporter atp7b binds and detoxifies cisplatin. Biochem J. 2009;419:51–6. 53 p following 56.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Dmitriev OY. Mechanism of tumor resistance to cisplatin mediated by the copper transporter atp7b. Biochem Cell Biol = Biochimie et biologie cellulaire. 2011;89:138–47.

    Article  CAS  Google Scholar 

  30. Safaei R, Otani S, Larson BJ, Rasmussen ML, Howell SB. Transport of cisplatin by the copper efflux transporter atp7b. Mol Pharmacol. 2008;73:461–8.

    Article  CAS  PubMed  Google Scholar 

  31. Katano K, Safaei R, Samimi G, Holzer A, Tomioka M, Goodman M, et al. Confocal microscopic analysis of the interaction between cisplatin and the copper transporter atp7b in human ovarian carcinoma cells. Clin Cancer Res: Off J Am Assoc Cancer Res. 2004;10:4578–88.

    Article  CAS  Google Scholar 

  32. Leonhardt K, Gebhardt R, Mossner J, Lutsenko S, Huster D. Functional interactions of cu-atpase atp7b with cisplatin and the role of atp7b in the resistance of cells to the drug. J Biol Chem. 2009;284:7793–802.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Baralle D, Baralle M. Splicing in action: assessing disease causing sequence changes. J Med Genet. 2005;42:737–48.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Buratti E, Baralle M, Baralle FE. Defective splicing, disease and therapy: searching for master checkpoints in exon definition. Nucleic Acids Res. 2006;34:3494–510.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Kim CH, Kim HS, Cubells JF, Kim KS. A previously undescribed intron and extensive 5' upstream sequence, but not phox2a-mediated transactivation, are necessary for high level cell type-specific expression of the human norepinephrine transporter gene. J Biol Chem. 1999;274:6507–18.

    Article  CAS  PubMed  Google Scholar 

  36. Klett CP, Bonner TI. Identification and characterization of the rat m1 muscarinic receptor promoter. J Neurochem. 1999;72:900–9.

    Article  CAS  PubMed  Google Scholar 

  37. Wu ZY, Wang N, Lin MT, Fang L, Murong SX, Yu L. Mutation analysis and the correlation between genotype and phenotype of arg778leu mutation in Chinese patients with Wilson disease. Arch Neurol. 2001;58:971–6.

    Article  CAS  PubMed  Google Scholar 

  38. Bucossi S, Polimanti R, Mariani S, Ventriglia M, Bonvicini C, Migliore S, et al. Association of k832r and r952k snps of Wilson's disease gene with Alzheimer's disease. J Alzheimer’s Dis : JAD. 2012;29:913–9.

    CAS  PubMed  Google Scholar 

  39. Schmid SC, Schuster T, Horn T, Gschwend J, Treiber U, Weirich G. Utility of atp7b in prediction of response to platinum-based chemotherapy in urothelial bladder cancer. Anticancer Res. 2013;33:3731–7.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank all subjects who volunteered to participate in this study. This work was supported by the National High-tech R&D Program of China (863 Program) (2012AA02A517), National Natural Science Foundation of China (81173129, 81202595, 81373490), Program for the Special Scientific Research Foundation of Doctor Disciplines in University of Ministry of Education of China (20110162110034), Hunan Provincial Natural Science Foundation of China (12JJ7006), and Hunan Provincial Science and Technology Plan Projects (2011TT2025, 2012TT2021).

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Authors and Affiliations

  1. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 410008, Changsha, People’s Republic of China

    Xiang-Ping Li, Ji-Ye Yin, Ying Wang, Hui He, Xi Li, Wei-Jing Gong, Juan Chen, Chen-Yue Qian, Yi Zheng, Yu Zhang, Ling Xiao, Hong-Hao Zhou & Zhao-Qian Liu

  2. Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, 410078, Changsha, People’s Republic of China

    Xiang-Ping Li, Ji-Ye Yin, Ying Wang, Hui He, Xi Li, Wei-Jing Gong, Juan Chen, Chen-Yue Qian, Yi Zheng, Yu Zhang, Ling Xiao, Hong-Hao Zhou & Zhao-Qian Liu

  3. Department of Pharmacy, Xiangya Hospital, Central South University, 410008, Changsha, People’s Republic of China

    Xiang-Ping Li, Tao Yin, Zhi-Cheng Gong & Bo-Ting Zhou

  4. The Affiliated Cancer Hospital of XiangYa School of Medicine, Central South University, 410014, Changsha, People’s Republic of China

    Fang Li

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  1. Xiang-Ping Li
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Correspondence to Zhao-Qian Liu.

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Li, XP., Yin, JY., Wang, Y. et al. The ATP7B genetic polymorphisms predict clinical outcome to platinum-based chemotherapy in lung cancer patients. Tumor Biol. 35, 8259–8265 (2014). https://doi.org/10.1007/s13277-014-2072-0

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  • DOI: https://doi.org/10.1007/s13277-014-2072-0

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