期刊论文详细信息
BMC Cancer
Osteopontin is a prognostic biomarker in non-small cell lung cancer
Ane Kongsgaard Rud5  Kjetil Boye7  Miriam Øijordsbakken4  Marius Lund-Iversen2  Ann Rita Halvorsen1  Steinar K Solberg3  Gisle Berge5  Åslaug Helland1  Odd Terje Brustugun1  Gunhild M Mælandsmo6 
[1] Department of Genetics, Institute for Cancer Research, The Norwegian Radium, Hospital, Oslo University Hospital, Oslo, Norway
[2] Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
[3] Department of Cardiovascular and Thoracic Surgery, Rikshospitalet, Oslo University Hospital, Oslo, Norway
[4] Department of Medical Biochemistry, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
[5] Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
[6] Department of Pharmacy, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway
[7] Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
关键词: S100A4;    Osteopontin;    Biomarker;    Prognosis;    NSCLC;   
Others  :  859258
DOI  :  10.1186/1471-2407-13-540
 received in 2013-06-25, accepted in 2013-11-07,  发布年份 2013
PDF
【 摘 要 】

Background

In a previously published report we characterized the expression of the metastasis-associated proteins S100A4, osteopontin (OPN) and ephrin-A1 in a prospectively collected panel of non-small cell lung cancer (NSCLC) tumors. The aim of the present follow-up study was to investigate the prognostic impact of these potential biomarkers in the same patient cohort. In addition, circulating serum levels of OPN were measured and single nucleotide polymorphisms (SNP) in the -443 position of the OPN promoter were analyzed.

Methods

Associations between immunohistochemical expression of S100A4, OPN and ephrin-A1 and relapse free and overall survival were examined using univariate and multivariate analyses. Serum OPN was measured by ELISA, polymorphisms in the -443 position of the tumor OPN promoter were analyzed by PCR, and associations between OPN levels and promoter polymorphisms and clinicopathological parameters and patient outcome were investigated.

Results

High expression of OPN in NSCLC tumors was associated with poor patient outcome, and OPN was a strong, independent prognostic factor for both relapse free and overall survival. Serum OPN levels increased according to tumor pT classification and tumor size, and patients with OPN-expressing tumors had higher serum levels than patients with OPN-negative tumors. S100A4 was a negative prognostic factor in several subgroups of adenocarcinoma patients, but not in the overall patient cohort. There was no association between ephrin-A1 expression and patient outcome.

Conclusions

OPN is a promising prognostic biomarker in NSCLC, and should be further explored in the selection of patients for adjuvant treatment following surgical resection.

【 授权许可】

   
2013 Rud et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20140724091923965.pdf 1035KB PDF download
47KB Image download
60KB Image download
【 图 表 】

【 参考文献 】
  • [1]Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin 2011, 61:69-90.
  • [2]Ishikawa M, Miyahara R, Sonobe M, Horiuchi M, Mennju T, Nakayama E, Kobayashi M, Kikuchi R, Kitamura J, Imamura N, et al.: Higher expression of EphA2 and ephrin-A1 is related to favorable clinicopathological features in pathological stage I non-small cell lung carcinoma. Lung Cancer 2012, 76:431-438.
  • [3]Goldstraw P, Ball D, Jett JR, Le Chevalier T, Lim E, Nicholson AG, Shepherd FA: Non-small-cell lung cancer. Lancet 2011, 378:1727-1740.
  • [4]Rud AK, Lund-Iversen M, Berge G, Brustugun OT, Solberg SK, Maelandsmo GM, Boye K: Expression of S100A4, ephrin-A1 and osteopontin in non-small cell lung cancer. BMC Cancer 2012, Aug 1, 12:333. BioMed Central Full Text
  • [5]Boye K, Maelandsmo GM: S100A4 and metastasis: a small actor playing many roles. Am J Pathol 2010, 176:528-535.
  • [6]Matsubara D, Niki T, Ishikawa S, Goto A, Ohara E, Yokomizo T, Heizmann CW, Aburatani H, Moriyama S, Moriyama H, et al.: Differential expression of S100A2 and S100A4 in lung adenocarcinomas: clinicopathological significance, relationship to p53 and identification of their target genes. Cancer Sci 2005, 96:844-857.
  • [7]Kimura K, Endo Y, Yonemura Y, Heizmann CW, Schafer BW, Watanabe Y, Sasaki T: Clinical significance of S100A4 and E-cadherin-related adhesion molecules in non-small cell lung cancer. Int J Oncol 2000, 16:1125-1131.
  • [8]Tsuna M, Kageyama S, Fukuoka J, Kitano H, Doki Y, Tezuka H, Yasuda H: Significance of S100A4 as a prognostic marker of lung squamous cell carcinoma. Anticancer Res 2009, 29:2547-2554.
  • [9]De Petris L, Orre LM, Kanter L, Pernemalm M, Koyi H, Lewensohn R, Lehtio J: Tumor expression of S100A6 correlates with survival of patients with stage I non-small-cell lung cancer. Lung Cancer 2009, 63:410-417.
  • [10]Feng J, Zhang X, Zhu H, Wang X, Ni S, Huang J: FoxQ1 overexpression influences poor prognosis in non-small cell lung cancer, associates with the phenomenon of EMT. PLoS One 2012, 7(6):e39937. doi: 10.1371/journal.pone.0039937. Epub 2012 Jun 28
  • [11]Wu J, Pungaliya P, Kraynov E, Bates B: Identification and quantification of osteopontin splice variants in the plasma of lung cancer patients using immunoaffinity capture and targeted mass spectrometry. Biomarkers 2012, 17:125-133.
  • [12]Zhao B, Sun T, Meng F, Qu A, Li C, Shen H, Jin Y, Li W: Osteopontin as a potential biomarker of proliferation and invasiveness for lung cancer. J Cancer Res Clin Oncol 2010, 137:1061-1070.
  • [13]Boldrini L, Donati V, Dell'Omodarme M, Prati MC, Faviana P, Camacci T, Lucchi M, Mussi A, Santoro M, Basolo F, Fontanini G: Prognostic significance of osteopontin expression in early-stage non-small-cell lung cancer. Br J Cancer 2005, 93:453-457.
  • [14]Donati V, Boldrini L, Dell'Omodarme M, Prati MC, Faviana P, Camacci T, Lucchi M, Mussi A, Santoro M, Basolo F, Fontanini G: Osteopontin expression and prognostic significance in non-small cell lung cancer. Clin Cancer Res 2005, 11:6459-6465.
  • [15]Weber GF, Lett GS, Haubein NC: Osteopontin is a marker for cancer aggressiveness and patient survival. Br J Cancer 2010, 103:861-869.
  • [16]Hu Z, Lin D, Yuan J, Xiao T, Zhang H, Sun W, Han N, Ma Y, Di X, Gao M, et al.: Overexpression of osteopontin is associated with more aggressive phenotypes in human non-small cell lung cancer. Clin Cancer Res 2005, 11:4646-4652.
  • [17]Schneider S, Yochim J, Brabender J, Uchida K, Danenberg KD, Metzger R, Schneider PM, Salonga D, Holscher AH, Danenberg PV: Osteopontin but not osteonectin messenger RNA expression is a prognostic marker in curatively resected non-small cell lung cancer. Clin Cancer Res 2004, 10:1588-1596.
  • [18]Chang YS, Kim HJ, Chang J, Ahn CM, Kim SK: Elevated circulating level of osteopontin is associated with advanced disease state of non-small cell lung cancer. Lung Cancer 2007, 57:373-380.
  • [19]Isa S, Kawaguchi T, Teramukai S, Minato K, Ohsaki Y, Shibata K, Yonei T, Hayashibara K, Fukushima M, Kawahara M, et al.: Serum osteopontin levels are highly prognostic for survival in advanced non-small cell lung cancer: results from JMTO LC 0004. J Thorac Oncol 2009, 4:1104-1110.
  • [20]Takenaka M, Hanagiri T, Shinohara S, Yasuda M, Chikaishi Y, Oka S, Shimokawa H, Nagata Y, Nakagawa M, Uramoto H: Serum level of osteopontin as a prognostic factor in patients who underwent surgical resection for non-small-cell lung cancer. Clin Lung Cancer 2012, 14(3):288-294. doi: 10.1016/j.cllc.2012.09.005. Epub 2012 Nov 1
  • [21]Giacopelli F, Marciano R, Pistorio A, Catarsi P, Canini S, Karsenty G, Ravazzolo R: Polymorphisms in the osteopontin promoter affect its transcriptional activity. Physiol Genomics 2004, 20:87-96.
  • [22]Pasquale EB: Eph receptors and ephrins in cancer: bidirectional signalling and beyond. Nat Rev Cancer 2010, 10:165-180.
  • [23]Saintigny P, Peng S, Zhang L, Sen B, Wistuba II, Lippman SM, Girard L, Minna JD, Heymach JV, Johnson FM: Global Evaluation of Eph receptors and ephrins in lung adenocarcinomas identifies EphA4 as an inhibitor of cell migration and invasion. Mol Cancer Ther 2012, 11:2021-2032.
  • [24]Flatmark K, Maelandsmo GM, Mikalsen SO, Nustad K, Varaas T, Rasmussen H, Meling GI, Fodstad O, Paus E: Immunofluorometric assay for the metastasis-related protein S100A4: release of S100A4 from normal blood cells prohibits the use of S100A4 as a tumor marker in plasma and serum. Tumour Biol 2004, 25:31-40.
  • [25]Bjorheim J, Gaudernack G, Giercksky KE, Ekstrom PO: Direct identification of all oncogenic mutants in KRAS exon 1 by cycling temperature capillary electrophoresis. Electrophoresis 2003, 24:63-69.
  • [26]Blasberg JD, Pass HI, Goparaju CM, Flores RM, Lee S, Donington JS: Reduction of elevated plasma osteopontin levels with resection of non-small-cell lung cancer. J Clin Oncol 2010, 28:936-941.
  • [27]Sharma P, Kumar S, Kundu GC: Transcriptional regulation of human osteopontin promoter by histone deacetylase inhibitor, trichostatin A in cervical cancer cells. Mol Cancer 2010, Jul 7, 9:178. doi: 10.1186/1476-4598-9-178 BioMed Central Full Text
  • [28]Shinohara ML, Kim HJ, Kim JH, Garcia VA, Cantor H: Alternative translation of osteopontin generates intracellular and secreted isoforms that mediate distinct biological activities in dendritic cells. Proc Natl Acad Sci USA 2008, 105:7235-7239.
  • [29]Lanteri P, Lombardi G, Colombini A, Grasso D, Banfi G: Stability of osteopontin in plasma and serum. Clin Chem Lab Med 2012, 50(11):1979-1984.
  • [30]Dong QZ, Zhang XF, Zhao Y, Jia HL, Zhou HJ, Dai C, Sun HJ, Qin Y, Zhang WD, Ren N, et al.: Osteopontin promoter polymorphisms at locus -443 significantly affect the metastasis and prognosis of human hepatocellular carcinoma. Hepatology 2013, 57:1024-1034.
  • [31]Schultz J, Lorenz P, Ibrahim SM, Kundt G, Gross G, Kunz M: The functional -443 T/C osteopontin promoter polymorphism influences osteopontin gene expression in melanoma cells via binding of c-Myb transcription factor. Mol Carcinog 2009, 48:14-23.
  • [32]Chen Y, Liu H, Wu W, Li Y, Li J: Osteopontin genetic variants are associated with overall survival in advanced non-small-cell lung cancer patients and bone metastasis. J Exp Clin Cancer Res 2013, Jul 24, 32:45. doi: 10.1186/1756-9966-32-45 BioMed Central Full Text
  文献评价指标  
  下载次数:30次 浏览次数:26次