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ARCHITECT® urine-neutrophil gelatinase-associated lipocalin (u-NGAL) assay as new prognostic marker for clear cell Renal Cell Carcinoma (ccRCC) (preliminary results)

International Urology and Nephrology volume 53, pages 59–67 (2021)Cite this article

Abstract

Introduction

Biomarkers for the diagnosis and monitoring treatment response of kidney cancer are urgently needed. Neutrophil gelatinase-associated lipocalin (NGAL) is a relevant urinary biomarker for the diagnosis of a wide variety of acute and chronic kidney diseases. Its potential utility as a prognostic marker of kidney cancer is largely unknown and, therefore, was the subject of this investigation.

Materials and methods

A retrospective study was done on 50 kidney tumor patients (urine samples prospectively collected before nephrectomy between 2004 and 2012, stored at Biobank Resource Center). The specificity, sensitivity and the predictive value of NGAL were determined for progression-free and disease-specific survival after nephrectomy in renal cell carcinoma (particularly, the clear cell renal cell carcinoma (ccRCC)). Urinary NGAL concentration (u-NGAL) was determined by CMIA technique (ARCHITECT® urine NGAL essay/ABBOTT®).

Results

Out of the 50 kidney tumor patients, 40 had clear cell carcinoma with a median u-NGAL excretion of 1.4 (IQR: 5.76) ng/mg urinary creatinine (Ucr). u-NGAL was correlated to tumor stage (p = 0.005), and Fuhrman grade (p = 0.0002). Multivariate Cox regression analysis showed a significant association between u-NGAL excretion and clear cell renal cell carcinoma progression free survival and disease specific survival (p = 0.002; p = 0.0001).

Conclusions

Urinary NGAL was significantly associated with the stage and the grade of kidney cancer. u-NGAL excretion could be considered as a potential biomarker to identify ccRCC patients with the more pejorative outcomes.

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References

  1. Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 67:7–30

    Article  Google Scholar 

  2. Cohen HT, McGovern FJ (2005) Renal-cell carcinoma. N Engl J Med 353:2477–2490

    CAS  PubMed  Article  Google Scholar 

  3. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ (2008) Cancer statistics, 2008. CA Cancer J Clin 58:71–96

    PubMed  Article  Google Scholar 

  4. Gill IS, Aron M, Gervais DA, Jewett MA (2010) Clinical practice. Small renal mass. N Engl J Med 362:624–634

    CAS  PubMed  Article  Google Scholar 

  5. Lippi G, Meschi T, Nouvenne A, Mattiuzzi C, Borghi L (2014) Neutrophil gelatinase-associated lipocalin in cancer. Adv Clin Chem 64:179–219

    CAS  PubMed  Article  Google Scholar 

  6. Friedl A, Stoesz SP, Buckley P, Gould MN (1999) Neutrophil gelatinase-associated lipocalin in normal and neoplastic human tissues. Cell type-specific pattern of expression. Histochem J 31:433–441

    CAS  PubMed  Article  Google Scholar 

  7. Perrin C, Patard JJ, Jouan F, Collet N, Theoleyre S, Edeline J, Zerrouki S, Laguerre B, Bellaud-Roturaud MA, Rioux-Leclercq N, Vigneau C (2011) La neutrophil gelatinase-associated lipocalin, ou LCN 2, facteur d’agressivité dans le carcinome rénale à cellules claires (CRCC). Prog Urol 21:851–858

    CAS  PubMed  Article  Google Scholar 

  8. Morrissey JJ, London AN, Lambert MC, Kharasch ED (2011) Sensitivity and specificity of urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 for the diagnosis of renal cell carcinoma. Am J Nephrol 34:391–398

    CAS  PubMed  Article  Google Scholar 

  9. Kovacs G, Akhtar M, Beckwith BJ, Bugert P, Cooper CS, Delahunt B, Eble JN, Fleming S, Ljungberg B, Medeiros LJ, Moch H, Reuter VE, Ritz E, Roos G, Schmidt D, Srigley JR, Störkel S, van den Berg E, Zbar B (1997) The Heidelberg classification of renal cell tumours. J Pathol 183(2):131–133

    CAS  PubMed  Article  Google Scholar 

  10. Fuhrman SA, Lasky LC, Limas C (1982) Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol 6(7):655–663

    CAS  PubMed  Article  Google Scholar 

  11. Edge SB, Byrd DR, Compton CC et al (2010) AJCC Cancer Staging Manual, 7th edn. Springier-Verlag, New York, NY

    Google Scholar 

  12. Wagener G, Lee HT (2009) In reply to ‘Instability of urinary NGAL during long-term storage’ and ‘NGAL and cardiac surgery-associated acute kidney injury’. Am J Kidney Dis 53:566

    Article  Google Scholar 

  13. Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16:31–41

    CAS  PubMed  Article  Google Scholar 

  14. Grenier FC, Ali S, Syed H, Workman R, Martens F, Liao M, Wang Y, Wong PY (2010) Evaluation of the ARCHITECT urine NGAL assay: assay performance, specimen handling requirements and biological variability. Clin Biochem 43(6):615–620

    CAS  PubMed  Article  Google Scholar 

  15. Chakraborty S, Kaur S, Guha S, Batra SK (2012) The multifaceted roles of neutrophil gelatinase associated lipocalin (NGAL) in inflammation and cancer. Biochim Biophys Acta 1826(1):129–169

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Cowland JB, Borregaard N (1997) Molecular characterization and pattern of tissue expression of the gene for neutrophil gelatinase-associated lipocalin from humans. Genomics 45(1):17–23

    CAS  PubMed  Article  Google Scholar 

  17. Yang J, Goetz D, Li JY, Wang W, Mori K, Setlik D, Du T, Erdjument-Bromage H, Tempst P, Strong R, Barasch J (2002) An iron delivery pathway mediated by a lipocalin. Mol Cell 10(5):1045–1056

    CAS  PubMed  Article  Google Scholar 

  18. Gwira JA, Wei F, Ishibe S (2005) Expression of neutrophil associated-gelatinase lipocalin regulates epithelial morphogenesis in vitro. J Biol Chem 280:7875–7882

    CAS  PubMed  Article  Google Scholar 

  19. Barresi V, Ieni A, Bolignano D, Magno C, Buemi M, Barresi G (2010) Neutrophil gelatinase-associated lipocalin immunoexpression in renal tumors: correlation with histotype and histological grade. Oncol Rep 24:305–310

    PubMed  Article  Google Scholar 

  20. Porta C, Paglino C, De AM, Quaglini S, Sacchi L, Imarisio I, Canipari C (2010) Predictive value of baseline serum vascular endothelial growth factor and neutrophil gelatinase-associated lipocalin in advanced kidney cancer patients receiving sunitinib. Kidney Int 77:809–815

    CAS  PubMed  Article  Google Scholar 

  21. Tong Z, Wu X, Ovcharenko D, Zhu J, Chen CS, Kehrer JP (2005) Neutrophil gelatinase-associated lipocalin as a survival factor. Biochem J 391:441–448

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  22. Hanai J, Mammoto T, Seth P, Mori K, Karumanchi SA, Barasch J, Sukhatme VP (2005) Lipocalin 2 diminishes invasiveness and metastasis of Ras-transformed cells. J Biol Chem 280(14):13641–13647

    CAS  PubMed  Article  Google Scholar 

  23. 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 288:1–10

    Article  Google Scholar 

  24. Devireddy LR, Gazin C, Zhu X, Green MR (2005) A cell-surface receptor for lipocalin 24p3 selectively mediates apoptosis and iron uptake. Cell 23:1293–1305

    Article  Google Scholar 

  25. Yan L, Borregaard N, Kjeldsen L, Moses MA (2001) The high molecular weight urinary matrix metalloproteinase (MMP) activity is a complex of gelatinase B/MMP-9 and neutrophil gelatinase-associated lipocalin (NGAL). Modulation of MMP-9 activity by NGAL. J Biol Chem 276:37258–37265

    CAS  PubMed  Article  Google Scholar 

  26. Bolignano D, Coppolino G, Lacquaniti A, Nicocia G, Buemi M (2008) Pathological and prognostic value of urinary neutrophil gelatinase-associated lipocalin (NGAL) in macroproteinuric patients with worsening renal function. Kidney Blood Press Res 31:274–279

    CAS  PubMed  Article  Google Scholar 

  27. Maeda A, Ando H, Ura T, Muro K, Aoki M, Saito K, Kondo E, Takahashi S, Ito Y, Mizuno Y, Fujimura A (2017) Differences in urinary renal failure biomarkers in cancer patients initially treated with cisplatin. Anticancer Res 37(9):5235–5239

    CAS  PubMed  Google Scholar 

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Funding

This work was funded by the patients’association “juste un petit rein”.

Author information

Affiliations

  1. Departments of Urology-Transplantation, Jules Verne University, CHU Amiens, 80000, Amiens, France

    Fabien Saint

  2. Nephrology, Jules Verne University, CHU Amiens, 80000, Amiens, France

    Gabriel Choukroun

  3. Pathology, Jules Verne University, CHU Amiens, 80000, Amiens, France

    Henri Sevestre

  4. Public Health and General Cancer Register de La Somme, Jules Verne University, CHU Amiens, 80000, Amiens, France

    Hajer Ben Khadhra

  5. Laboratory of Biochemistry, Jules Verne University, CHU Amiens, 80000, Amiens, France

    Françoise Rose-Robert

  6. EPROAD EA 4669, Jules Verne University, CHU Amiens, 80000, Amiens, France

    Carole Amant & Fabien Saint

  7. BRC (Biobanque de Picardie), Jules Verne University, CHU Amiens, 80000, Amiens, France

    Yves Edouard Herpe & Fabien Saint

  8. Association “Juste Un Petit Rein”, Jules Verne University, CHU Amiens, 80000, Amiens, France

    Luc Catherine

Authors
  1. Hajer Ben Khadhra
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  2. Françoise Rose-Robert
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  3. Yves Edouard Herpe
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  4. Henri Sevestre
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  5. Gabriel Choukroun
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  6. Luc Catherine
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  7. Carole Amant
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  8. Fabien Saint
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Contributions

All the authors made substantial contributions to this work. BKH: data analysis/manuscript writing. RRF: data collection or management. HYE: data collection or management. SH: data collection. GC: data collection. LC: project development. AC: data collection or management. SF: protocol/project development/data collection/manuscript writing.

Corresponding author

Correspondence to Fabien Saint.

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The authors declare that they have no conflict of interest.

Research involving human participants

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Bioethics Committee of the Medical Jules Verne University (No. GASPATU/ CNIL 822859; CHU T204).

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Informed consent was obtained from all individual participants included in the study.

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Ben Khadhra, H., Rose-Robert, F., Herpe, Y.E. et al. ARCHITECT® urine-neutrophil gelatinase-associated lipocalin (u-NGAL) assay as new prognostic marker for clear cell Renal Cell Carcinoma (ccRCC) (preliminary results). Int Urol Nephrol 53, 59–67 (2021). https://doi.org/10.1007/s11255-020-02604-w

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  • DOI: https://doi.org/10.1007/s11255-020-02604-w

Keywords

  • Clear cell renal carcinoma
  • NGAL
  • Urinary markers