Serum NGAL and S100A12 as Biomarkers of Active Disease in Ulcerative Colitis

Orhan Çiçek; Fatih Kamış; Özge Kurtkulağı; Yavuz Beyazıt

doi:10.19161/etd.1754910

TR EN

Ülseratif Kolitte Aktif Hastalığın biyobelirteçleri olarak serum NGAL ve S100A12

Abstract

Amaç: Bu çalışmada, ülseratif kolit (ÜK) hastalarında serum nötrofil jelatinaz ilişkili lipokalin (NGAL) ve S100A12 (S100 kalsiyum bağlayıcı protein A12) düzeylerinin hastalık aktivitesinin belirlenmesinde biyobelirteç olarak kullanılabilirliğinin aynı çalışma kapsamında araştırılması amaçlandı. Gereç ve Yöntem: Çalışmaya, aynı ÜK hastalarının aktif (n=34) ve remisyon (n=34) dönemlerinde değerlendirilen bireyler ile kontrol grubu (n=31) dahil edildi. Klinik ve endoskopik olarak ÜK tanısı alan hastalardan ve kontrol grubundan venöz kan örnekleri alınarak NGAL ve S100A12 düzeyleri ile rutin laboratuvar parametreleri analiz edildi. Tüm demografik ve klinik değişkenler gruplar arasında karşılaştırıldı. Bulgular: Aktif ülseratif kolit hastalarında serum NGAL ve S100A12 düzeyleri, remisyon dönemindeki hastalara ve kontrol grubuna kıyasla belirgin şekilde daha yüksek bulundu (sırasıyla p = 0.001 ve p <0.001). Aktif ÜK’yı saptamak amacıyla yapılan ROC analizinde, NGAL ve S100A12 en uygun kesim değerlerinde yüksek duyarlılık ve özgüllük gösterdi (p <0.001). Kontrol grubu referans alınarak yapılan multinomiyal lojistik regresyon analizinde hem NGAL hem de S100A12 düzeyleri aktif grupta; S100A12 düzeyleri ise remisyon grubunda, ayarlanmamış ve ayarlanmış modellerde aktif hastalık varlığı ile anlamlı şekilde ilişkili kaldı. Bu belirteçlerdeki her bir birimlik artış aktif hastalık olasılığını anlamlı ölçüde artırdı (tüm karşılaştırmalar için p <0.05). Sonuç: Bu çalışmada, aktif ÜK grubunda serum NGAL ve S100A12 düzeylerinin remisyon ve kontrol gruplarına kıyasla belirgin şekilde yüksek olduğu gösterilmiştir. Daha geniş kapsamlı çalışmalara ihtiyaç vardır.

Keywords

Serum NGAL and S100A12 as Biomarkers of Active Disease in Ulcerative Colitis

Abstract

Aim: To investigate the potential use of serum neutrophil gelatinase-associated lipocalin (NGAL) and S100A12 (S100 calcium-binding protein A12) as biomarkers for determining disease activity in ulcerative colitis (UC) within the same study. Materials and Methods: The study included individuals from the active (n=34) and remission (n=34) periods of the same UC patients, as well as a control group (n=31). Venous blood samples were collected from patients with clinically and endoscopically diagnosed UC and from the control group to analyze NGAL and S100A12 levels, in addition to routine laboratory tests. All demographic and clinical variables were compared between the groups. Results: Patients with active ulcerative colitis exhibited markedly higher serum NGAL and S100A12 concentrations than those in remission or the control group (p = 0.001 and p < 0.001, respectively). In the ROC analysis performed to detect active UC, NGAL and S100A12 showed high sensitivity and specificity at their optimal cut-off values (p<0.001). In the multinomial logistic regression analysis with the control group as the reference, both NGAL and S100A12 levels in the active group, and S100A12 levels in the remission group, remained significantly associated with active disease in both unadjusted and adjusted models. Each unit increase in these markers significantly increased the likelihood of active disease (p<0.05 for all comparisons). Conclusions: In this study, serum NGAL and S100A12 concentrations were markedly elevated in the active UC group relative to the remission and control groups. Larger studies are needed.

Keywords

References

1. Berry SK, Melmed GY. Quality indicators in inflammatory bowel disease. Intestinal research. 2018;16(1):43-7.
2. Lichtenstein GR, Loftus EV, Isaacs KL, Regueiro MD, Gerson LB, Sands BE. ACG clinical guideline: management of Crohn's disease in adults. Am J Gastroenterol. 2018;113(4):481-517.
3. Sands BE. From symptom to diagnosis: clinical distinctions among various forms of intestinal inflammation. Gastroenterology. 2004;126(6):1518-32.
4. Satsangi J, Silverberg M, Vermeire S, Colombel J. The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut. 2006;55(6):749-53.
5. Ng SC, Shi HY, Hamidi N, Underwood FE, Tang W, Benchimol EI, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. The Lancet. 2017;390(10114):2769-78.
6. Ince MN, Elliott DE. Effective use of the laboratory in the management of patients with inflammatory bowel diseases. Gastroenterol Clin North. 2019;48(2):237-58.
7. Borkham‐Kamphorst E, Drews F, Weiskirchen R. Induction of lipocalin‐2 expression in acute and chronic experimental liver injury moderated by pro‐inflammatory cytokines interleukin‐1β through nuclear factor‐κB activation. Liver International. 2011;31(5):656-65.
8. Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, et al. Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol.. 2003;14(10):2534-43.

9. Yndestad A, Landrø L, Ueland T, Dahl CP, Flo TH, Vinge LE, et al. Increased systemic and myocardial expression of neutrophil gelatinase-associated lipocalin in clinical and experimental heart failure. Eur Heart J.. 2009;30(10):1229-36.
10. Korkmaz H, Asil M, Temel T, Öztürk B, Kebapcilar L. Evaluation of serum neutrophil gelatinase-associated lipocalin (NGAL), asymmetricdimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) levels, and theirrelations with disease type and activity in inflammatory bowel diseases. Turk J Med Sci.. 2021;51(5):2403-12.
11. Komosinska-Vassev K, Kałużna A, Jura-Półtorak A, Derkacz A, Olczyk K. Circulating profile of ECM-related proteins as diagnostic markers in inflammatory bowel diseases. J Clin Med.. 2022;11(19):5618.
12. Oikonomou K, Kapsoritakis A, Theodoridou C, Karangelis D, Germenis A, Stefanidis I, et al. Neutrophil gelatinase-associated lipocalin (NGAL) in inflammatory bowel disease: association with pathophysiology of inflammation, established markers, and disease activity. J Gastroenterol.. 2012;47(5):519-30.
13. Abozeid F, Ali K, Bahgat M, Maher M, Borg AM. Assessing the activity of Inflammatory Bowel Disease using the serum marker: Neutrophil Gelatinase Associated Lipocalin (NGAL). Mansoura Medical Journal. 2023;53(1):2.
14. Meijer B, Gearry R, Day A. The role of S100A12 as a systemic marker of inflammation. Int J Inflam.. 2012;2012(1):907078.
15. Donato R, Cannon BR, Sorci G, Riuzzi F, Hsu K, J Weber D, et al. Functions of S100 proteins. Curr Mol Med. 2013;13(1):24-57.
16. Heizmann CW, Fritz G, Schafer B. S100 proteins: structure, functions and pathology. Front Biosci (Landmark Ed)) 2002;7(1):1356-68.
17. Guignard F, Mauel J, Markert M. Identification and characterization of a novel human neutrophil protein related to the S100 family. Biochem J. 1995;309(2):395-401.
18. Foell D, Kucharzik T, Kraft M, Vogl T, Sorg C, Domschke W, et al. Neutrophil derived human S100A12 (EN-RAGE) is strongly expressed during chronic active inflammatory bowel disease. Gut. 2003;52(6):847-53.
19. Levy I, Gralnek IM. Complications of diagnostic colonoscopy, upper endoscopy, and enteroscopy. Best Pract Res Clin Gastroenterol. 2016;30(5):705-18.
20. Horiuchi I, Horiuchi K, Horiuchi A, Umemura T. Serum leucine-rich α2 glycoprotein could be a useful biomarker to differentiate patients with normal colonic mucosa from those with inflammatory bowel disease or other forms of colitis. J Clin Med. 2024;13(10):2957.
21. Aghsaeifard Z, Alizadeh R, Bagheri N. Association between neutrophil gelatinase-associated lipocalin (NGAL) and iron profile in chronic renal disease. Arch Physiol Biochem.2022;128(3):703-7.
22. Elshereef HK, Helbawi FM, Mahmoud ME, Abdelwahab HM. Serum neutrophil gelatinase-associated lipocalin as promising diagnostic marker and a predictor of activity of ulcerative colitis patients: single center study. Egypt J Haematol.. 2024;49(1):108-14.
23. Nooh M, Mohammed H, Taiel S, El Hagary H. Study of serum neutrophil gelatinase-associated lipocalin level in inflammatory bowel disease patients. Menoufia Med J. 2018;31(2):600-.
24. Thorsvik S, Damås JK, Granlund Av, Flo TH, Bergh K, Østvik AE, et al. Fecal neutrophil gelatinase‐associated lipocalin as a biomarker for inflammatory bowel disease. J Gastroenterol Hepatol.2017;32(1):128-35.
25. Yeşil A, Gönen C, Şenateş E, Paker N, Gökden Y, Koçhan K, et al. Relationship between neutrophil gelatinase-associated lipocalin (NGAL) levels and inflammatory bowel disease type and activity. Dig Dis Sci. 2013;58(9):2587-93.
26. Hofmann MA, Drury S, Fu C, Qu W, Taguchi A, Lu Y, et al. RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell. 1999;97(7):889-901.
27. Kaur A, Goggolidou P. Ulcerative colitis: understanding its cellular pathology could provide insights into novel therapies. Inflamm (Lond). 2020;17(1):15.
28. Kałużna A, Jura-Półtorak A, Derkacz A, Jaruszowiec J, Olczyk K, Komosinska-Vassev K. Circulating profiles of serum proguanylin, S100A12 protein and Pentraxin 3 as diagnostic markers of ulcerative colitis. J Clin Med. 2023;12(13):4339.
29. Kaiser T, Langhorst J, Wittkowski H, Becker K, Friedrich AW, Rueffer A, et al. Faecal S100A12 as a non-invasive marker distinguishing inflammatory bowel disease from irritable bowel syndrome. Gut. 2007;56(12):1706-13.
30. Zhang Q, Zuo Y, Xu M. The correlation of serum vaspin, S100A12 and PCT levels with the severity of ulcerative colitis and its clinical significance. Am J Transl Res. 2021;13(7):7914.

Details

Primary Language

English

Subjects

Gastroenterology and Hepatology, Internal Diseases

Journal Section

Research Article

Authors

Orhan Çiçek ^*
0000-0003-1918-8544
Türkiye

Fatih Kamış
0000-0003-2913-6166
Türkiye

Özge Kurtkulağı
0000-0002-4162-5563
Türkiye

Yavuz Beyazıt
0000-0001-6247-2714
Türkiye

Publication Date

September 3, 2026

Submission Date

August 8, 2025

Acceptance Date

March 24, 2026

Published in Issue

Year 2026 Volume: 65 Number: 3

DOI

https://doi.org/10.19161/etd.1754910

IZ

https://izlik.org/JA23LU99ZL

Cite

RIS / Bibtex

APA

Çiçek, O., Kamış, F., Kurtkulağı, Ö., & Beyazıt, Y. (2026). Serum NGAL and S100A12 as Biomarkers of Active Disease in Ulcerative Colitis. Ege Tıp Dergisi, 65(3), 376-385. https://doi.org/10.19161/etd.1754910

AMA

1.Çiçek O, Kamış F, Kurtkulağı Ö, Beyazıt Y. Serum NGAL and S100A12 as Biomarkers of Active Disease in Ulcerative Colitis. EJM. 2026;65(3):376-385. doi:10.19161/etd.1754910

Chicago

Çiçek, Orhan, Fatih Kamış, Özge Kurtkulağı, and Yavuz Beyazıt. 2026. “Serum NGAL and S100A12 As Biomarkers of Active Disease in Ulcerative Colitis”. Ege Tıp Dergisi 65 (3): 376-85. https://doi.org/10.19161/etd.1754910.

EndNote

Çiçek O, Kamış F, Kurtkulağı Ö, Beyazıt Y (September 1, 2026) Serum NGAL and S100A12 as Biomarkers of Active Disease in Ulcerative Colitis. Ege Tıp Dergisi 65 3 376–385.

IEEE

[1]O. Çiçek, F. Kamış, Ö. Kurtkulağı, and Y. Beyazıt, “Serum NGAL and S100A12 as Biomarkers of Active Disease in Ulcerative Colitis”, EJM, vol. 65, no. 3, pp. 376–385, Sept. 2026, doi: 10.19161/etd.1754910.

ISNAD

Çiçek, Orhan - Kamış, Fatih - Kurtkulağı, Özge - Beyazıt, Yavuz. “Serum NGAL and S100A12 As Biomarkers of Active Disease in Ulcerative Colitis”. Ege Tıp Dergisi 65/3 (September 1, 2026): 376-385. https://doi.org/10.19161/etd.1754910.

JAMA

1.Çiçek O, Kamış F, Kurtkulağı Ö, Beyazıt Y. Serum NGAL and S100A12 as Biomarkers of Active Disease in Ulcerative Colitis. EJM. 2026;65:376–385.

MLA

Çiçek, Orhan, et al. “Serum NGAL and S100A12 As Biomarkers of Active Disease in Ulcerative Colitis”. Ege Tıp Dergisi, vol. 65, no. 3, Sept. 2026, pp. 376-85, doi:10.19161/etd.1754910.

Vancouver

1.Orhan Çiçek, Fatih Kamış, Özge Kurtkulağı, Yavuz Beyazıt. Serum NGAL and S100A12 as Biomarkers of Active Disease in Ulcerative Colitis. EJM. 2026 Sep. 1;65(3):376-85. doi:10.19161/etd.1754910