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NGAL and NGALR are frequently overexpressed in human gliomas and are associated with clinical prognosis

  • Laboratory Investigation - Human/Animal Tissue
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Abstract

Recently, neutrophil gelatinase-associated lipocalin (NGAL) and its cell surface receptor, NGALR, have been shown to have critical roles in the biology of various tumors. Therefore, we investigated the expression of NGAL and NGALR in tumor sections obtained from patients with gliomas, and compared these results with the clinical characteristics of the patients. Using immunohistochemical assays, the expression levels of NGAL and NGALR were found to be up-regulated in tumor tissues, and to be related to tumor grade (p < 0.001). A positive correlation between expression of the two markers was also observed in these assays (r = 0.849; p < 0.001). Overexpression of NGAL and NGALR in glioma tissues was also confirmed in western blot analysis and real-time quantitative RT-PCR assays. Furthermore, overexpression of NGAL and NGALR was found to be significantly associated with poor prognosis (p < 0.001 in each case). Multivariate analysis identified patient age, tumor grade, and expression levels of NGAL and NGALR to be independent prognostic factors. In particular, NGAL(2+)/NGALR(2+) tissues were associated with lower rates of survival (risk ratio, 1.378; 95% CI, 1.102–1.724; p = 0.005). These findings suggest that NGAL and NGALR expression are frequently up-regulated in gliomas, and are closely associated with poor clinical outcome.

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References

  1. Louis DN, Ohgaki H, Wiestler OD et al (2007) The 2007 WHO classifcation of tumours of the central nervous system. Acta Neuropathol 114:97–109

    Article  PubMed  Google Scholar 

  2. Deangelis LM (2001) Brain tumors. N Engl J Med 344:114–123

    Article  PubMed  CAS  Google Scholar 

  3. Flower DR (1996) The lipocalin protein family: structure and function. Biochem J 318:1–14

    PubMed  CAS  Google Scholar 

  4. Goetz DH, Holmes MA, Borregaard N, Bluhm ME, Raymond KN, Strong RK (2002) The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol Cell 10:1033–1043

    Article  PubMed  CAS  Google Scholar 

  5. Yang J, Goetz D, Li JY et al (2002) An iron delivery pathway mediated by a lipocalin. Mol Cell 10:1045–1056

    Article  PubMed  CAS  Google Scholar 

  6. Bolignano D, Donato V, Lacquaniti A et al (2010) Neutrophil gelatinase-associated lipocalin (NGAL) in human neoplasias: a new protein enters the scene. Cancer Lett 288:10–16

    Article  PubMed  CAS  Google Scholar 

  7. Xu S, Venge P (2000) Lipocalins as biochemical markers of disease. Biochim Biophys Acta 1482:298–307

    Article  PubMed  CAS  Google Scholar 

  8. Devireddy LR, Gazin C, Zhu X, Green MR (2005) A cell-surface receptor for lipocalin 24p3 selectively mediates apoptosis and iron uptake. Cell 123:1293–1305

    Article  PubMed  CAS  Google Scholar 

  9. Richardson DR (2005) Molecular mechanisms of iron uptake by cells and the use of iron chelators for the treatment of cancer. Curr Med Chem 12:2711–2729

    Article  PubMed  CAS  Google Scholar 

  10. Kaplan J (2002) Mechanisms of cellular iron acquisition: another iron in the fire. Cell 111:603–606

    Article  PubMed  CAS  Google Scholar 

  11. Hung YC, Huang GS, Lin LW, Hong MY, Se PS (2007) Thea sinensis melanin prevents cisplatin-induced nephrotoxicity in mice. Food Chem Toxicol 45:1123–1130

    Article  PubMed  CAS  Google Scholar 

  12. Mori K, Lee HT, Rapoport D et al (2005) Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury. J Clin Invest 115:610–621

    PubMed  CAS  Google Scholar 

  13. Bauer M, Eickhoff JC, Gould MN, Mundhenke C, Maass N, Friedl A (2008) Neutrophil gelatinase-associated lipocalin (NGAL) is a predictor of poor prognosis in human primary breast cancer. Breast Cancer Res Treat 108:389–397

    Article  PubMed  CAS  Google Scholar 

  14. Iannetti A, Pacifico F, Acquaviva R et al (2008) The neutrophil gelatinase-associated lipocalin(NGAL), a NF-kappaB-regulated gene, is a survival factor for thyroid neoplastic cells. Proc Natl Acad Sci USA 105:14058–14063

    Article  PubMed  CAS  Google Scholar 

  15. Kubben FJ, Sier CF, Hawinkels LJ et al (2007) Clinical evidence for a protective role of lipocalin-2 against MMP-9 autodegradation and the impact for gastric cancer. Eur J Cancer 43:1869–1876

    Article  PubMed  CAS  Google Scholar 

  16. Zhang H, Xu L, Xiao D et al (2007) Upregulation of neutrophil gelatinase-associated lipocalin in oesophageal squamous cell carcinoma: significant correlation with cell differentiation and tumour invasion. J Clin Pathol 60:555–561

    Article  PubMed  CAS  Google Scholar 

  17. Cui L, Xu LY, Shen ZY et al (2008) NGALR is overexpressed and regulated by hypomethylation in esophageal squamous cell carcinoma. Clin Cancer Res 14:7674–7681

    Article  PubMed  CAS  Google Scholar 

  18. Fang WK, Xu LY, Lu XF et al (2007) A novel alternative spliced variant of neutrophil gelatinase-associated lipocalin receptor in oesophageal carcinoma cells. Biochem J 403:297–303

    Article  PubMed  CAS  Google Scholar 

  19. Hutterer M, Knyazev P, Abate A et al (2008) Axl and growth arrest-specific gene 6 are frequently overexpressed in human gliomas and predict poor prognosis in patients with glioblastoma multiforme. Clin Cancer Res 14:130–138

    Article  PubMed  CAS  Google Scholar 

  20. Remmele W, Schicketanz KH (1993) Immunohistochemical determination of estrogen and progesterone receptor content in human breast cancer. Computer-assisted image analysis (QIC score) versus subjective grading (IRS). Pathol Res Pract 189:862–866

    PubMed  CAS  Google Scholar 

  21. Bratt T (2000) Lipocalins and cancer. Biochim Biophys Acta 1482:318–326

    Article  PubMed  CAS  Google Scholar 

  22. Sheng Z, Wang SZ, Green MR (2009) Transcription and signalling pathways involved in BCR–ABL-mediated misregulation of 24p3 and 24p3R. EMBO J 28:866–876

    Article  PubMed  CAS  Google Scholar 

  23. Bolignano D, Donato V, Coppolino G et al (2008) Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage. Am J Kidney Dis 52:595–605

    Article  PubMed  CAS  Google Scholar 

  24. Devarajan P (2008) NGAL in acute kidney injury: from serendipity to utility. Am J Kidney Dis 52:395–399

    Article  PubMed  Google Scholar 

  25. Stoesz SP, Friedl A, Haag JD, Lindstrom MJ, Clark GM, Gould MN (1998) Heterogeneous expression of the lipocalin NGAL in primary breast cancers. Int J Cancer 79:565–572

    Article  PubMed  CAS  Google Scholar 

  26. Smith ER, Manfredi M, Scott RM, Black PM, Moses MA (2007) A recurrent craniopharyngioma illustrates the potential usefulness of urinary matrix metalloproteinases as noninvasive biomarkers: case report. Neurosurgery 60:E1148–E1149 (Discussion E1149)

    Article  PubMed  Google Scholar 

  27. Smith ER, Zurakowski D, Saad A, Scott RM, Moses MA (2008) Urinary biomarkers predict brain tumor presence and response to therapy. Clin Cancer Res 14:2378–2386

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Shao-Hong Wang, Xiu-E Xu and Xiao-Fen Zhan for technical assistance, and Qing Zhao for data management. This study was supported by grants from the National High Technology Research and Development Program of China 863 Program grant (2006AA02A403); National Natural Science Foundation of China grants (30672376) and Guangdong Scientific Fund Key Items grants (7118419). The authors have no personal financial or institutional interest in any of the drugs, materials, or devices described in this article.

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Authors and Affiliations

  1. Department of Neurosurgery, Affiliated Shantou Hospital of Sun Yat-Sen University, Shantou, China

    Ming-Fa Liu & Tao Jin

  2. Department of Pathology, Affiliated Shantou Hospital of Sun Yat-Sen University, Shantou, China

    Jin-Hui Shen

  3. Institute of Oncologic Pathology, Medical College of Shantou University, Shantou, China

    Zhong-Ying Shen

  4. Department of Pathology, Second Affiliated Hospital of Shantou University, Shantou, China

    Zhi-Chao Zheng

  5. Department of Neurosurgery, Second Affiliated Hospital of Shantou University, Shantou, China

    Zeng-Liang Zhang

  6. Institute of Oncologic Pathology, Medical College of Shantou University, Shantou, China

    Li-Yan Xu

  7. Department of Biochemistry and Molecular Biology, Medical College of Shantou University, Shantou, China

    En-Min Li

  8. Department of Neurosurgery, Affiliated Shantou Hospital of Sun Yat-Sen University, No. 114, Wai Ma Road, Shantou, 515041, Guangdong, China

    Hai-Xiong Xu

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  1. Ming-Fa Liu
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  2. Tao Jin
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  3. Jin-Hui Shen
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  7. Li-Yan Xu
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  9. Hai-Xiong Xu
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Corresponding authors

Correspondence to Ming-Fa Liu or Hai-Xiong Xu.

Additional information

Ming-Fa Liu and Tao Jin contributed equally to this work.

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11060_2010_486_MOESM1_ESM.tif

Fig. 6 A Kaplan–Meier plot showing the relationship between NGAL protein expression and the survival of patients. The results showed that there was no statistically significant in each subgroup (TIFF 2334 kb)

11060_2010_486_MOESM2_ESM.tif

Fig. 7 A Kaplan–Meier plot showing the relationship between NGALR protein expression and the survival of patients. The results showed that NGALR expression appeared to be prognostic only in grade I–II (a) (TIFF 2334 kb)

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Liu, MF., Jin, T., Shen, JH. et al. NGAL and NGALR are frequently overexpressed in human gliomas and are associated with clinical prognosis. J Neurooncol 104, 119–127 (2011). https://doi.org/10.1007/s11060-010-0486-0

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  • DOI: https://doi.org/10.1007/s11060-010-0486-0

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