Neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9) prognostic value in lung adenocarcinoma
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Prognosis in patients with lung cancer is poor. Neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9) are proteins involved in the invasion and metastases of cancer. The objective of this study is to determine if there is a relationship between tumor expression of NGAL and MMP-9 in lung adenocarcinoma patients with prognosis and overall survival. Retrospective analysis was made of patients with lung adenocarcinoma treated at Medica Sur Hospital between 2005 and 2013. Tumor tissue was analyzed for NGAL and MMP-9 expression by immunohistochemistry. We identified 41 patients. Mean overexpression in tumoral tissue of NGAL was 70 % and 30 % for MMP-9. Univariate analysis revealed that prognostic factors associated with overall survival (OS) were NGAL expression and stage at diagnosis. Median OS for NGAL expression <70 % was 45.7 months (95 % CI; 15.2–76.2) and for patients with ≥70 % 4.6 months (95 % CI; 0.5–18.8; P < 0.0001), and for stage at diagnosis (stages I and II mean not reached), stage III mean OS 15.57 months (95 % CI; 9.8–21.2) and stage IV 9.6 months (95 % CI; 0.8–18.4. P = 0.002). No differences in OS were found for expression of MMP-9. Multivariate analysis revealed significance for OS in NGAL expression (HR 5.01 [95 % CI; 1.68–14.93] P = 0.004) and stage at diagnosis (HR 2.05 [95 % CI 1.30–3.22] P = 0.002). Tumoral tissue expression of NGAL ≥70 % confers a worse prognosis compared to those who did not. NGAL is an independent prognostic factor of stage at diagnosis.
KeywordsLipocalin Lepidic Adenocarcinoma Matrix metalloproteinase
Neutrophil gelatinase-associated lipocalin
Conflicts of interest
All procedures performed were in accordance with the ethical standards of the institutional committee. For this type of study, formal consent is not required.
- 1.GLOBOCAN. International Agency for Research on Cancer. Cancer incidence and mortality worldwide in 2012. Globocan cancer fact sheets: lung cancer 2014. http://globocan.iarc.fr/. Accessed 17 June 2012.
- 2.Goldstraw P, Crowley J, Chansky K, Giroux DJ, Groome PA, Rami-Porta R, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol Off Publ Int Assoc Stud Lung Cancer. 2007;2(8):706–14. doi: 10.1097/JTO.0b013e31812f3c1a.Google Scholar
- 3.National Comprehensive Cancer Network. Occult primary (version 1.2015). 2014. http://www.nccn.org/professionals/physician_gls/pdf/occult.pdf. Accessed 28 Oct 2014.
- 5.Wenners AS, Mehta K, Loibl S, Park H, Mueller B, Arnold N, et al. Neutrophil gelatinase-associated lipocalin (NGAL) predicts response to neoadjuvant chemotherapy and clinical outcome in primary human breast cancer. PLoS One. 2012;7(10):e45826. doi: 10.1371/journal.pone.0045826.CrossRefPubMedPubMedCentralGoogle Scholar
- 7.Barresi V, Reggiani-Bonetti L, Di Gregorio C, Vitarelli E, Ponz De Leon M, Barresi G. Neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9) prognostic value in stage I colorectal carcinoma. Pathol Res Pract. 2011;207(8):479–86. doi: 10.1016/j.prp.2011.05.012.CrossRefPubMedGoogle Scholar
- 9.Fernandez CA, Yan L, Louis G, Yang J, Kutok JL, Moses MA. The matrix metalloproteinase-9/neutrophil gelatinase-associated lipocalin complex plays a role in breast tumor growth and is present in the urine of breast cancer patients. Clin Cancer Res Off J Am Assoc Cancer Res. 2005;11(15):5390–5. doi: 10.1158/1078-0432.CCR-04-2391.CrossRefGoogle Scholar
- 11.Villalba Caloca J, Martínez Heredero R. Frecuencia del carcinoma broncopulmonar en pacientes fumadores y no fumadores diagnosticados en el Instituto Nacional de Enfermedades Respiratorias en el año 2001. Rev Inst Nac Enferm Respiratorias. 2004;17:27–34.Google Scholar
- 13.Postoperative T1 N0 non-small cell lung cancer. Squamous versus nonsquamous recurrences. The Lung Cancer Study Group. J Thorac Cardiovasc Surg. 1987;94(3):349–54.Google Scholar
- 16.Ruffini E, Asioli S, Filosso PL, Buffoni L, Bruna MC, Mossetti C, et al. Significance of the presence of microscopic vascular invasion after complete resection of Stage I-II pT1-T2N0 non-small cell lung cancer and its relation with T-size categories: did the 2009 7th edition of the TNM staging system miss something? J Thorac Oncol Off Publ Int Assoc Stud Lung Cancer. 2011;6(2):319–26. doi: 10.1097/JTO.0b013e3182011f70.Google Scholar
- 23.Shinriki S, Jono H, Ueda M, Obayashi K, Nakamura T, Ota K, et al. Stromal expression of neutrophil gelatinase-associated lipocalin correlates with poor differentiation and adverse prognosis in oral squamous cell carcinoma. Histopathology. 2014;64(3):356–64. doi: 10.1111/his.12293.CrossRefPubMedGoogle Scholar
- 28.Provatopoulou X, Gounaris A, Kalogera E, Zagouri F, Flessas I, Goussetis E, et al. Circulating levels of matrix metalloproteinase-9 (MMP-9), neutrophil gelatinase-associated lipocalin (NGAL) and their complex MMP-9/NGAL in breast cancer disease. BMC Cancer. 2009;9:390. doi: 10.1186/1471-2407-9-390.CrossRefPubMedPubMedCentralGoogle Scholar
- 30.Tong Z, Kunnumakkara AB, Wang H, Matsuo Y, Diagaradjane P, Harikumar KB, et al. Neutrophil gelatinase-associated lipocalin: a novel suppressor of invasion and angiogenesis in pancreatic cancer. Cancer Res. 2008;68(15):6100–8. doi: 10.1158/0008-5472.can-08-0540.CrossRefPubMedPubMedCentralGoogle Scholar
- 31.Yan L, Borregaard N, Kjeldsen L, Moses MA. 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. 2001;276(40):37258–65. doi: 10.1074/jbc.M106089200.CrossRefPubMedGoogle Scholar
- 47.Hu L, Hittelman W, Lu T, Ji P, Arlinghaus R, Shmulevich I, et al. NGAL decreases E-cadherin-mediated cell-cell adhesion and increases cell motility and invasion through Rac1 in colon carcinoma cells. Lab Investig J Tech Methods Pathol. 2009;89(5):531–48. doi: 10.1038/labinvest.2009.17.CrossRefGoogle Scholar