Serum cystatin C as a biomarker in non-Hodgkin lymphoma and its relationship with paraoxonase 1 activity

  • Bosa Mirjanić-Аzaric Department of Medical Biochemistry, Faculty of Medicine, University of Banja Luka, Banja Luka, The Republic of Srpska, Bosnia and herzegovina
  • Smiljana Mijic Aqualab laboratory, Banja Luka, The Republic of Srpska
  • Zana Radic Savic Department of Medical Biochemistry, Faculty of Medicine, University of Banja Luka, Banja Luka, The Republic of Srpska
  • Sinisa Stankovic Faculty of Medicine, University of Banja Luka, Banja Luka, Republic of Srpska
  • Dragana Malcic-Zanic Faculty of Medicine, University of Banja Luka, Banja Luka, Republic of Srpska
  • Natasa Mihailovic Egeljic Faculty of Medicine, University of Banja Luka, Banja Luka, Republic of Srpska
  • Đorđe Stojisavljevic Faculty of Medicine, University of Banja Luka, Banja Luka, Republic of Srpska
  • Bojana ivetic Institute of Laboratory Diagnostic, University Clinical Centre of the Republic of Srpska, Banja Luka
  • Natasa Bogavac-Stanojevic Department of Medical Biochemistry, University of Belgrade-Faculty of Pharmacy, Belgrade,
DOI: https://doi.org/10.5937/jomb0-61502
Keywords: Cystatin C, Paraoxonase 1, non-Hodgkin lymphoma

Abstract


Background: The aim of this pilot study was to assess the potential of cystatin C (Cys C) as a biomarker in NHL and to explore its association with paraoxonase 1 (PON1) activity.  Methods: The study included 44 patients with B-cell NHL and 44 healthy subjects. Cys C was measured using the Cobas e 801 analyzer (Roche Diagnostics GmbH, Mannheim, Germany), while PON1and TAS were measured on the ILab 300+ system (Instrumentation Laboratory, Milan, Italy).

Results: The serum level of Cys C (mg/L) was significantly higher in NHL patients compared to control subjects :1.03 (0.88–1.24)           vs 0.83 (0.78–0.90), P     <0.001. The diagnostic performance of Cys C, as assessed by the area under the ROC curve (AUC), was 0.812 (95% CI: 0.732–0.902). The optimal cut-off value for Cys C was 0.870 mg/L with a sensitivity and specificity of 77.1% and 75.6%, respectively. A significant negative correlation was observed between Cys C and PON1 activity (r = –0.42, P = 0.010) in NHL patients.

Conclusions: This study underscores the potential of Cys C as a biomarker in NHL. Notably, in the multivariable analysis, Cys C emerged as the only significant predictor of the disease, with each unit increase associated with an approximately threefold higher odds of NHL. Furthermore, the negative correlation between Cys C and PON1, identified for the first time in patients with NHL, may offer valuable insights for future research into the molecular mechanisms underlying this malignancy.

References

1. Mussap M, Plebani M. Biochemistry and clinical role of human cystatin C. Critical Reviews in Clinical Laboratory Sciences 2004; 41(5–6): 467-550.
2. Fernando S, Polkinghorne KR. Cystatin C: not just a marker of kidney function. J Bras Nefrol 2020; 42 (1):6-7.
3. Breznik B, Mitrović A, T Lah T, Kos J. Cystatins in cancer progression: More than just cathepsin inhibitors. Biochimie 2019; 166:233-250.
4. Huang C, Lu J, Yang J, Wang Z, Hang D, Fu Z. Associations of serum cystatin C concentrations with total mortality and mortality of 12 site-specific cancers. Front Oncol 2024; 14:1405879.
5. Corbeanu R.I, Găman A.M. The Involvement of Oxidative Stress in Non-Hodgkin’s Lymphomas; A Review of the Literature. J Mind Med Sci 2022; 9(1): 1-15.
6. Litvinov D, Mahini H, Garelnabi M. Antioxidant and anti-inflammatory role of paraoxonase 1: implication in arteriosclerosis diseases. N Am J Med Sci 2012; 4(11):523-32.
7. Vavlukis M, Vavlukis A, Krsteva K, Topuzovska S. Paraoxonase 1 gene polymorphisms in lipid oxidation and atherosclerosis development. Front Genet 2022; 13:966413.
8. Mirjanic-Azaric B, Stankovic S, Nezic L, Radic Savic Z, Malcic-Zanic D, Skrbic R, et al. Analysis of redox status and HDL sublasses in patients with lymphoma and the associations with FDG-PET/CT findings. Front Oncol 2023; 13:1221414.
9. Mugnaini E.N, Ghosh N. Lymphoma. Prim Care 2016; 43(4): 661–75.
10. Mengting Z, Yuekang X. Involvement of cystatin C in immunity and apoptosis. Immunol Lett 2018; 196:80-90.
11. Leto G, Crescimanno M, Flandina C. On the role of cystatin C in cancer progression. Life Sci 2018; 202:152-160.
12. Richter R, Furlong CE. Determination of paraoxonase (PON1) status requires more than genotyping. Pharmacogenetics 1999; 9(6):745-53.
13. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 2004; 37(4):277-85.
14. Mirjanić-Azarić B, Stanković S, Radić Savić Z, Malčić Zanić D, Ninić A, Vuković M, et al. Assessment of the diagnostic value of serum cathepsin S and its correlation with HDL subclasses in patients with Non-Hodgkin’s lymphoma. J Med Biochem 2024; 43(5):711-9.
15. Hammouda NE, Salah El-Din MA, El-Shishtawy MM, El-Gayar AM. Serum cystatin C as a biomarker in diffuse large B-Cell lymphoma. Sci Pharm 2017; 85(1):9.
16. Nishio C, Yoshida K, Nishiyama K, Hatanaka H, Yamada M. Involvement of cystatin C in oxidative stress induced apoptosis of cultured rat CNS neurons. Brain Res 2000; 873(2): 252-62.
17. Softić A, Begić L, Halilbasić A, Kos J. Cystatin C in sera of patients with aggressive non-Hodgkin B-cell lymphoma. Med Glas (Zenica) 2011; 8(1):97-100.
18. Balci H, Genc H, Papila C, Can G, Papila B, Yanardag H, et al. Serum lipid hydroperoxide levels and paraoxonase activity in patients with lung, breast, and colorectal cancer. J Clin Lab Anal 2012; 26 (3):155-60.
19. Özdemir Başer Ö, Göçmen AY, Aydoğan Kırmızı D. The role of inflammation, oxidation and Cystatin C in the pathophysiology of polycystic ovary syndrome. Turk J Obstet Gynecol 2022; 19(3):229-35.
20. Varga E, Seres I, Harangi M, Sztanek F, Asztalos L, Lõcsey L, et al. Serum cystatin C is a determinant of paraoxonase activity in hemodialyzed and renal transplanted patients. Dis Markers 2009; 26(3):141-8.
21. Zi M, Xu Y. Involvement of cystatin C in immunity and apoptosis. Immunol Lett 2018; 196:80-90.
22. Lu S, Li S. Association between preoperative serum Cystatin C levels and postsurgical
oncological prognosis in patients with PRCC: A retrospective cohort study. Cancer Med 2022; 11(22):4112-21.
23. Wyss M, Kaddurah-Daouk R. Creatine and creatinine metabolism. Physiol Rev 2000; 80(3):1107–213.
24. Wang Y, Branicky R, Noë A, Hekimi S. Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling. J Cell Biol 2018; 217(6):1915–28.
25. Bojic S, Kotur-Stevuljevic J, Kalezic N, Jelic-Ivanovic Z, Stefanovic A, Palibrk I, et al. Low paraoxonase 1 activity predicts mortality in surgical patients with sepsis. Dis Markers 2014:2014:427378.
26. Jozanov-Stankov O, Đuric J, Dobutovic B, Isenovic E. Determination of total antioxidant status (TAS) as a biochemical parameter in control of workers' health. Arch Biol Sci 2009; 61(3): 375-82.
Published
2026/03/03
Issue
Ahead of print
Section
Original paper

Copyright (c) 2026 Bosa Mirjanić-Аzaric, Smiljana Mijic, Zana Radic Savic, Sinisa Stankovic, Dragana Malcic-Zanic, Natasa Mihailovic Egeljic, Đorđe Stojisavljevic, Bojana ivetic, Natasa Bogavac-Stanojevic

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