期刊论文详细信息
BMC Cancer
A case–control study of pre-operative levels of serum neutrophil gelatinase-associated lipocalin and other potential inflammatory markers in colorectal cancer
Claire Bonithon-Kopp7  Jean-Michel Petit2  Sophie Deguelte-Lardière4  Jean-Baptiste Delhorme5  Georges Mantion1  Marie-Lorraine Scherrer6  Abderrahmane Bourredjem7  Pablo Ortega-Deballon3  Laurence Duvillard8 
[1]Department of general, digestive and oncologic surgery, University hospital of Besançon, Besançon 25030-F, France
[2]Inserm UMR 866, Faculté de médecine de Dijon, Dijon 21079-F, France
[3]Department of digestive surgical oncology, University hospital of Dijon, Dijon 21000-F, France
[4]Department of general, digestive and endocrine surgery, University hospital of Reims, Reims 51100-F, France
[5]Department of general and digestive surgery, Hôpital de Hautepierre, University hospital of Strasbourg, Strasbourg 67098-F, France
[6]Department of general and digestive surgery, Hôpital Brabois, University hospital of Nancy, Vandoeuvre-les-Nancy, Nancy 54511-F, France
[7]Clinical investigation center (team clinical epidemiology), University hospital of Dijon, Dijon 21000-F, France
[8]Biochemistry department, University hospital of Dijon, Dijon 21070-F, France
关键词: sTNFR-2;    sTNFR-1;    NGAL/MMP-9;    NGAL;    Inflammation;    CRP;    Case–control study;    Colorectal cancer;   
Others  :  1117951
DOI  :  10.1186/1471-2407-14-912
 received in 2014-04-04, accepted in 2014-11-20,  发布年份 2014
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【 摘 要 】

Background

Chronic inflammation is a key feature of colorectal cancer (CRC), meaning that inflammatory biomarkers may be useful for its diagnosis. In particular, high neutrophil gelatinase-associated lipocalin (NGAL) expression has been reported in CRC. Thus, we investigated whether serum NGAL and NGAL/MMP-9 could be potential biomarkers for the early detection of CRC. Concurrently, we studied other inflammatory biomarkers such as soluble tumor necrosis factor receptor 1 and 2 (sTNFR-1, sTNFR-2), and C reactive protein (CRP).

Methods

The AGARIC multicenter case–control study was performed in eastern France and included patients admitted for elective surgery either for a priori non-metastatic incident CRC (n = 224) or for benign causes (n = 252). Pre-operative serum levels of NGAL, NGAL/MMP-9, sTNFR-1, sTNFR-2 and CRP were measured.

Results

Median values of serum NGAL, NGAL/MMP-9, sTNFR-1, sTNFR-2 and CRP were significantly higher in CRC patients than in controls. Receiver Operating Characteristic analysis provided relatively poor values of area under the curve, ranging from 0.65 to 0.58. Except for NGAL/MMP-9, all biological parameters were strongly correlated in CRC cases and, less strongly in controls. Multivariate odds ratio (OR) of CRC comparing the extreme tertiles of serum NGAL was 2.76 (95% confidence interval (CI): 1.59-4.78; p < 0.001),. Lower but significant multivariate associations were observed for sTNFR-1, and sTNFR-2: OR = 2.44 (95% CI : 1.34-4.45, p = 0.015) and 1.93 (95% : CI 1.12-3.31), respectively. No independent association was found between case–control status and NGAL/MMP-9. Among CRC cases, maximal tumor size was an independent determinant of serum NGAL (p = 0.028) but this association was reduced after adjustment for CRP (p = 0.11).

Conclusion

Despite a significant increase in serum NGAL and other inflammatory markers among CRC patients, our findings suggest that they may not be suitable biomarkers for the diagnosis and especially early detection of CRC.

【 授权许可】

   
2014 Duvillard et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010, 2010(127):2893-2917.
  • [2]Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin 2011, 61(2):69-90.
  • [3]Sanjoaquin MA, Choodari-Oskooei B, Dolbear C, Putcha V, Sehgal A, Key TJ, Møller H: Colorectal cancer incidence, mortality and survival in South-east England between 1972 and 2001. Eur J Cancer Prev 2007, 16(1):10-16.
  • [4]Kjeldsen L, Johnsen AH, Sengeløv H, Borregaard N: Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase. J Biol Chem 1993, 268:10425-10432.
  • [5]Roudkenar MH, Halabian R, Ghasemipour Z, Roushandeh AM, Rouhbakhsh M, Nekogoftar M, Kuwahara Y, Fukumoto M, Shokrgozar MA: Neutrophil gelatinase-associated lipocalin acts as a protective factor against H(2)O(2) toxicity. Arch Med Res 2008, 39(6):560-566.
  • [6]Bahmani P, Halabian R, Rouhbakhsh M, Roushandeh AM, Masroori N, Ebrahimi M, Samadikuchaksaraei A, Shokrgozar MA, Roudkenar MH: Neutrophil gelatinase-associated lipocalin induces the expression of heme oxygenase-1 and superoxide dismutase 1, 2. Cell Stress Chaperones 2010, 15(4):395-403.
  • [7]Aujla SJ, Chan YR, Zheng M, Fei M, Askew DJ, Pociask DA, Reinhart TA, McAllister F, Edeal J, Gaus K, Husain S, Kreindler JL, Dubin PJ, Pilewski JM, Myerburg MM, Mason CA, Iwakura Y, Kolls JK: IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. Nat Med 2008, 14(3):275-281.
  • [8]Nairz M, Theurl I, Schroll A, Theurl M, Fritsche G, Lindner E, Seifert M, Crouch ML, Hantke K, Akira S, Fang FC, Weiss G: Absence of functional Hfe protects mice from invasive Salmonella enterica serovar Typhimurium infection via induction of lipocalin-2. Blood 2009, 114(17):3642-3651.
  • [9]Nomura I, Gao B, Boguniewicz M, Darst MA, Travers JB, Leung DY: Distinct patterns of gene expression in the skin lesions of atopic dermatitis and psoriasis: a gene microarray analysis. J Allergy Clin Immunol 2003, 112:1195-1202.
  • [10]Van Dyke TE, Schweinebraten M, Cianciola LJ, Offenbacher S, Genco RJ: Neutrophil chemotaxis in families with localized juvenile periodontitis. J Periodontal Res 1985, 20:503-514.
  • [11]Ding L, Hanawa H, Ota Y, Hasegawa G, Hao K, Asami F, Watanabe R, Yoshida T, Toba K, Yoshida K, Ogura M, Kodama M, Aizawa Y: Lipocalin-2/neutrophil gelatinase-B associated lipocalin is strongly induced in hearts of rats with autoimmune myocarditis and in human myocarditis. Circ J 2010, 74(3):523-530.
  • [12]Yndestad A, Landrø L, Ueland T, Dahl CP, Flo TH, Vinge LE, Espevik T, Frøland SS, Husberg C, Christensen G, Dickstein K, Kjekshus J, Øie E, Gullestad L, Aukrust P: Increased systemic and myocardial expression of neutrophil gelatinase-associated lipocalin in clinical and experimental heart failure. Eur Heart J 2009, 30(10):1229-1236.
  • [13]Galamb O, Györffy B, Sipos F, Spisák S, Németh AM, Miheller P, Tulassay Z, Dinya E, Molnár B: Inflammation, adenoma and cancer: objective classification of colon biopsy specimens with gene expression signature. Dis Markers 2008, 25(1):1-16.
  • [14]Oikonomou KA, Kapsoritakis AN, Theodoridou C, Karangelis D, Germenis A, Stefanidis I, Potamianos SP: Neutrophil gelatinase-associated lipocalin (NGAL) in inflammatory bowel disease: association with pathophysiology of inflammation, established markers, and disease activity. J Gastroenterol 2012, 47(5):519-530.
  • [15]Sahinarslan A, Kocaman SA, Bas D, Akyel A, Ercin U, Zengin O, Timurkaynak T: Plasma neutrophil gelatinase-associated lipocalin levels in acute myocardial infarction and stable coronary artery disease. Coron Artery Dis 2011, 22(5):333-338.
  • [16]Bu DX, Hemdahl AL, Gabrielsen A, Fuxe J, Zhu C, Eriksson P, Yan ZQ: Induction of neutrophil gelatinase-associated lipocalin in vascular injury via activation of nuclear factor-kappaB. Am J Pathol 2006, 169(6):2245-2253.
  • [17]El-Mesallamy HO, Hamdy NM, Zaghloul AS, Sallam AM: Clinical value of circulating lipocalins and insulin-like growth factor axis in pancreatic cancer diagnosis. Pancreas 2013, 42(1):149-154.
  • [18]Wang HJ, He XJ, Ma YY, Jiang XT, Xia YJ, Ye ZY, Zhao ZS, Tao HQ: Expressions of neutrophil gelatinase-associated lipocalin in gastric cancer: a potential biomarker for prognosis and an ancillary diagnostic test. Anat Rec (Hoboken) 2010, 293(11):1855-1863.
  • [19]Iannetti A, Pacifico F, Acquaviva R, Lavorgna A, Crescenzi E, Vascotto C, Tell G, Salzano AM, Scaloni A, Vuttariello E, Chiappetta G, Formisano S, Leonardi A: The neutrophil gelatinase-associated lipocalin (NGAL), a NF-kappaB-regulated gene, is a survival factor for thyroid neoplastic cells. Proc Natl Acad Sci U S A 2008, 05(37):14058-14063.
  • [20]Miyamoto T, Kashima H, Suzuki A, Kikuchi N, Konishi I, Seki N, Shiozawa T: Laser-captured microdissection-microarray analysis of the genes involved in endometrial carcinogenesis: stepwise up-regulation of lipocalin2 expression in normal and neoplastic endometria and its functional relevance. Hum Pathol 2011, 42(9):1265-1274.
  • [21]Sung H, Choi JY, Lee SA, Lee KM, Han S, Jeon S, Song M, Lee Y, Park SK, Yoo KY, Noh DY, Ahn SH, Kang D: The association between the preoperative serum levels of lipocalin-2 and matrix metalloproteinase-9 (MMP-9) and prognosis of breast cancer. BMC Cancer 2012, 12:193. BioMed Central Full Text
  • [22]Wenners AS, Mehta K, Loibl S, Park H, Mueller B, Arnold N, Hamann S, Weimer J, Ataseven B, Darb-Esfahani S, Schem C, Mundhenke C, Khandan F, Thomssen C, Jonat W, Holzhausen HJ, von Minckwitz G, Denkert C, Bauer M: Neutrophil gelatinase-associated lipocalin (NGAL) predicts response to neoadjuvant chemotherapy and clinical outcome in primary human breast cancer. PLoS One 2012, 7(10):e45826.
  • [23]Yang J, Bielenberg DR, Rodig SJ, Doiron R, Clifton MC, Kung AL, Strong RK, Zurakowski D, Moses MA: Lipocalin 2 promotes breast cancer progression. Proc Natl Acad Sci U S A 2009, 106(10):3913-3918.
  • [24]Bauer M, Eickhoff JC, Gould MN, Mundhenke C, Maass N, Friedl A: Neutrophil gelatinase-associated lipocalin (NGAL) is a predictor of poor prognosis in human primary breast cancer. Breast Cancer Res Treat 2008, 108(3):389-397.
  • [25]Cho H, Kim JH: Lipocalin2 expressions correlate significantly with tumor differentiation in epithelial ovarian cancer. J Histochem Cytochem 2009, 57(5):513-521.
  • [26]Porta C, Paglino C, De Amici M, Quaglini S, Sacchi L, Imarisio I, Canipari C: Predictive value of baseline serum vascular endothelial growth factor and neutrophil gelatinase-associated lipocalin in advanced kidney cancer patients receiving sunitinib. Kidney Int 2010, 77(9):809-815.
  • [27]Sun Y, Yokoi K, Li H, Gao J, Hu L, Liu B, Chen K, Hamilton SR, Fan D, Sun B, Zhang W: NGAL expression is elevated in both colorectal adenoma-carcinoma sequence and cancer progression and enhances tumorigenesis in xenograft mouse models. Clin Cancer Res 2011, 17(13):4331-4340.
  • [28]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):479-486.
  • [29]Barresi V, Di Gregorio C, Reggiani-Bonetti L, Ieni A, Ponz-De Leon M, Barresi G: Neutrophil gelatinase-associated lipocalin: a new prognostic marker in stage I colorectal carcinoma? Hum Pathol 2011, 42(11):1720-1726.
  • [30]Marti J, Fuster J: Prognostic value of serum neutrophil gelatinase-associated lipocalin in metastatic and non-metastatic colorectal cancer: reply. World J Surg 2013, 37(11):2729.
  • [31]Fung KY, Priebe I, Purins L, Tabor B, Brierley GV, Lockett T, Nice E, Gibbs P, Tie J, McMurrick P, Moore J, Ruszkiewicz A, Burgess A, Cosgrove LJ: Performance of serum lipocalin 2 as a diagnostic marker for colorectal cancer. Cancer Biomark 2013, 13(2):75-79.
  • [32]Candido S, Maestro R, Polesel J, Catania A, Maira F, Signorelli SS, McCubrey JA, Libra M: Roles of neutrophil gelatinase-associated lipocalin (NGAL) in human cancer. Oncotarget 2014, 5(6):1576-1594.
  • [33]Yan L, Borregaard N, Kjeldsen L, Moses MA 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):37258-37265.
  • [34]Toriola AT, Cheng TY, Neuhouser ML, Wener MH, Zheng Y, Brown E, Miller JW, Song X, Beresford SA, Gunter MJ, Caudill MA, Ulrich CM: Biomarkers of inflammation are associated with colorectal cancer risk in women but are not suitable as early detection markers. Int J Cancer 2013, 132(11):2648-2658.
  • [35]Bünger S, Haug U, Kelly M, Posorski N, Klempt-Giessing K, Cartwright A, Fitzgerald SP, Toner V, McAleer D, Gemoll T, Laubert T, Büning J, Fellermann K, Bruch HP, Roblick UJ, Brenner H, von Eggeling F, Habermann JK: A novel multiplex-protein array for serum diagnostics of colon cancer: a case–control study. BMC Cancer 2012, 12:393. BioMed Central Full Text
  • [36]Aleksandrova K, Jenab M, Boeing H, Jansen E, Bueno-de-Mesquita HB, Rinaldi S, Riboli E, Overvad K, Dahm CC, Olsen A, Tjønneland A, Boutron-Ruault MC, Clavel-Chapelon F, Morois S, Palli D, Krogh V, Tumino R, Vineis P, Panico S, Kaaks R, Rohrmann S, Trichopoulou A, Lagiou P, Trichopoulos D, van Duijnhoven FJ, Leufkens AM, Peeters PH, Rodríguez L, Bonet C, Sánchez MJ, et al.: Circulating C-reactive protein concentrations and risks of colon and rectal cancer: a nested case–control study within the European Prospective Investigation into Cancer and Nutrition. Am J Epidemiol 2010, 172(4):407-418.
  • [37]Youden WJ: Index for rating diagnostic tests. Cancer 1950, 3(1):32-35.
  • [38]Little RJA, Rubin DB: Statistical Analysis with Missing Data. 2nd edition. New York 20: John Wiley & Sons; 2002.
  • [39]Haase-Fielitz A, Bellomo R, Devarajan P, Story D, Matalanis G, Dragun D, Haase M: Novel and conventional serum biomarkers predicting acute kidney injury in adult cardiac surgery–a prospective cohort study. Crit Care Med 2009, 37(2):553-560.
  • [40]Constantin JM, Futier E, Perbet S, Roszyk L, Lautrette A, Gillart T, Guerin R, Jabaudon M, Souweine B, Bazin JE, Sapin V: Plasma neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in adult critically ill patients: a prospective study. J Crit Care 2010, 25(1):176. e1-6
  • [41]McLean MH, Thomson AJ, Murray GI, Fyfe N, Hold GL, El-Omar EM: Expression of neutrophil gelatinase-associated lipocalin in colorectal neoplastic progression a marker of malignant potential? Br J Cancer 2013, 108(12):2537-2541.
  • [42]Bousserouel S, Kauntz H, Gossé F, Bouhadjar M, Soler L, Marescaux J, Raul F: Identification of gene expression profiles correlated to tumor progression in a preclinical model of colon carcinogenesis. Int J Oncol 2010, 36(6):1485-1490.
  • [43]Nielsen BS, Borregaard N, Bundgaard JR, Timshel S, Sehested M: Kjeldsen : Induction of NGAL synthesis in epithelial cells of human colorectal neoplasia and inflammatory bowel diseases. Gut 1996, 38(3):414-420.
  • [44]Hu L, Hittelman W, Lu T, Ji P, Arlinghaus R, Shmulevich I, Hamilton SR, Zhang W: NGAL decreases E-cadherin-mediated cell-cell adhesion and increases cell motility and invasion through Rac1 in colon carcinoma cells. Lab Invest 2009, 89:531-548.
  • [45]Karlsen JR, Borregaard N, Cowland JB: Induction of neutrophil gelatinase-associated lipocalin expression by co-stimulation with interleukin-17 and tumor necrosis factor-alpha is controlled by IkappaB-zeta but neither by C/EBP-beta nor C/EBP-delta. J Biol Chem 2010, 285:14088-14100.
  • [46]Landrø L, Damås JK, Flo TH, Heggelund L, Ueland T, Tjønnfjord GE, Espevik T, Aukrust P, Frøland SS: Decreased serum lipocalin-2 levels in human immunodeficiency virus-infected patients: increase during highly active anti-retroviral therapy. Clin Exp Immunol 2008, 152(1):57-63.
  • [47]Bando M, Hiroshima Y, Kataoka M, Shinohara Y, Herzberg MC, Ross KF, Nagata T, Kido J: Interleukin-1alpha regulates antimicrobial peptide expression in human keratinocytes. Immunol Cell Biol 2007, 85(7):532-537.
  • [48]Chan AT, Ogino S, Giovannucci EL, Fuchs CS: Inflammatory markers are associated with risk of colorectal cancer and chemopreventive response to anti-inflammatory drugs. Gastroenterology 2011, 140(3):799-808.
  • [49]Song M, Wu K, Ogino S, Fuchs CS, Giovannucci EL, Chan AT: A prospective study of plasma inflammatory markers and risk of colorectal cancer in men. Br J Cancer 2013, 108(9):1891-1898.
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