title: Aurora-A contributes to cisplatin resistance and lymphatic metastasis in non-small cell lung cancer and predicts poor prognosis.
abstract: BACKGROUND
  Platinum-based chemotherapy improves survival among patients with non-small cell lung cancer (NSCLC), but the efficiency is limited due to resistance. In this study, we aimed to identify the expression of Aurora-A and its correlation with cisplatin resistance and prognosis in NSCLC.
  
  
  METHODS
  We used immunohistochemical analysis to determine the expression of Aurora-A protein in 102 NSCLC patients treated by surgery and adjuvant cisplatin-based chemotherapy. The prognostic significances were assessed by Kaplan-Meier survival estimates and Cox models. The potential role of Aurora-A in the regulation of cisplatin resistance in NSCLC cells was examined by transfections using expression vector and small interfering RNA or using small-molecule inhibitors.
  
  
  RESULTS
  Aurora-A expression was significantly associated with clinical stage (p = 0.018), lymph node metastasis (p = 0.038) and recurrence (p = 0.005), and was an independent prognostic parameter in multivariate analysis. High level of Aurora-A expression predicted poorer overall survival (OS) and progression-free survival (PFS). In vitro data showed that Aurora-A expression was elevated in cisplatin-resistant lung cancer cells, and overexpression or knockdown of Aurora-A resulted in increased or decreased cellular resistance to cisplatin. Furthermore, inhibition of Aurora-A reversed the migration ability of cisplatin-resistant cells.
  
  
  CONCLUSIONS
  The current findings suggest that high Aurora-A expression is correlated with cisplatin-based chemotherapeutic resistance and predicts poor patient survival in NSCLC. Aurora-A might serve as a predictive biomarker of drug response and therapeutic target to reverse chemotherapy resistance.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Cai-feng
authors.initials: CF
authors.lastname: Yue
authors.forename: Wei-hua
authors.initials: WH
authors.lastname: Zhou
authors.forename: Yuan-min
authors.initials: YM
authors.lastname: Qian
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China. wsw_2003@163.com.
authors.forename: Shao-wu
authors.initials: SW
authors.lastname: Wang
authors.forename: An-wen
authors.initials: AW
authors.lastname: Liu
authors.forename: Quentin
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D064096:Aurora Kinase A / Q000235:genetics / Q000502:physiology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000627:therapeutic use*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D064096:Aurora Kinase A; D002945:Cisplatin
references.citation: Cancer Res Treat. 2012 Sep;44(3):151-6
references.pmid: 23091440
references.citation: Clin Cancer Res. 2005 Mar 1;11(5):1827-34
references.pmid: 15756006
references.citation: Cancer Res. 2009 Mar 15;69(6):2400-7
references.pmid: 19276344
references.citation: N Engl J Med. 2013 Mar 21;368(12):1101-10
references.pmid: 23514287
references.citation: Cancer. 2010 Aug 1;116(15):3645-55
references.pmid: 20564088
references.citation: Nat Rev Cancer. 2013 Oct;13(10):714-26
references.pmid: 24060863
references.citation: Cancer Biol Ther. 2009 Oct;8(20):1914-21
references.pmid: 20009541
references.citation: Cancer Res. 2007 Nov 1;67(21):10436-44
references.pmid: 17974987
references.citation: J Natl Compr Canc Netw. 2006 Jul;4(6):548-82
references.pmid: 16813724
references.citation: N Engl J Med. 2004 Jan 22;350(4):379-92
references.pmid: 14736930
references.citation: Ann Thorac Surg. 2006 Feb;81(2):440-6; discussion 446-7
references.pmid: 16427828
references.citation: Cell Cycle. 2009 Jul 15;8(14):2132-3
references.pmid: 19556872
references.citation: J Clin Pathol. 2007 Oct;60(10):1112-6
references.pmid: 17182662
references.citation: J Clin Oncol. 2014 Jan 1;32(1):44-50
references.pmid: 24043741
references.citation: Biochem Biophys Res Commun. 2007 Jan 5;352(1):220-5
references.pmid: 17113039
references.citation: Lung Cancer. 2010 Jun;68(3):478-83
references.pmid: 19683826
references.citation: FEBS Lett. 2011 Jun 23;585(12):1884-90
references.pmid: 21557940
references.citation: Cancer Cell. 2003 Jan;3(1):51-62
references.pmid: 12559175
references.citation: Clin Cancer Res. 2008 Jan 15;14(2):435-45
references.pmid: 18223218
references.citation: Autophagy. 2012 Mar;8(3):389-400
references.pmid: 22240664
references.citation: Clin Cancer Res. 2003 Apr;9(4):1420-6
references.pmid: 12684414
references.citation: Int J Cancer. 2006 Nov 15;119(10):2304-12
references.pmid: 16894566
references.citation: Mol Cancer Ther. 2012 Mar;11(3):763-74
references.pmid: 22302096
references.citation: PLoS One. 2013;8(2):e56919
references.pmid: 23437271
references.citation: Cancer Res. 2009 Jul 15;69(14):5820-8
references.pmid: 19584296
references.citation: Ann Thorac Surg. 2011 Nov;92(5):1794-804; discussion 1804
references.pmid: 22051275
references.citation: Clin Cancer Res. 2003 Mar;9(3):991-7
references.pmid: 12631597
references.citation: Gynecol Oncol. 2012 Oct;127(1):63-9
references.pmid: 22772063
references.citation: Int J Oncol. 2007 Aug;31(2):277-83
references.pmid: 17611683
references.citation: Cancer Res. 2010 Jun 1;70(11):4655-65
references.pmid: 20460511
references.citation: Cancer. 2009 Nov 15;115(22):5143-54
references.pmid: 19658185
references.citation: Biochim Biophys Acta. 2009 Dec;1796(2):75-90
references.pmid: 19306912
references.citation: CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
references.pmid: 21296855
references.citation: J Int Med Res. 2008 Jul-Aug;36(4):734-47
references.pmid: 18652770
references.citation: Ann Surg Oncol. 2010 Jun;17(6):1471-4
references.pmid: 20180029
references.citation: J Transl Med. 2008 Dec 11;6:79
references.pmid: 19077237
references.citation: Cell Res. 2006 Apr;16(4):356-66
references.pmid: 16617331
references.citation: Nat Rev Drug Discov. 2005 Apr;4(4):307-20
references.pmid: 15789122
references.citation: Cancer Res. 1999 May 1;59(9):2041-4
references.pmid: 10232583
references.citation: Carcinogenesis. 2008 Oct;29(10):1930-7
references.pmid: 18667445
references.citation: Nat Commun. 2014 Apr 17;5:3661
references.pmid: 24739462
references.citation: Nat Genet. 1998 Oct;20(2):189-93
references.pmid: 9771714
references.citation: Cancer Res. 2010 Nov 15;70(22):9118-28
references.pmid: 21045147
references.citation: Cell. 2012 Jul 6;150(1):165-78
references.pmid: 22770218
references.citation: Mol Cancer Ther. 2010 Feb;9(2):268-78
references.pmid: 20124450
references.citation: EMBO J. 1998 Jun 1;17(11):3052-65
references.pmid: 9606188
references.citation: Nat Rev Cancer. 2005 Jan;5(1):42-50
references.pmid: 15630414
references.citation: Biochim Biophys Acta. 2010 Oct-Dec;1799(10-12):829-39
references.pmid: 20863917