Cancer Management and Research (Aug 2021)

Association of Tumour Microenvironment with Protein Glycooxidation, DNA Damage, and Nitrosative Stress in Colorectal Cancer

  • Zińczuk J,
  • Zaręba K,
  • Kamińska J,
  • Koper-Lenkiewicz OM,
  • Dymicka-Piekarska V,
  • Pryczynicz A,
  • Guzińska-Ustymowicz K,
  • Kędra B,
  • Matowicka-Karna J,
  • Żendzian-Piotrowska M,
  • Zalewska A,
  • Maciejczyk M

Journal volume & issue
Vol. Volume 13
pp. 6329 – 6348

Abstract

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Justyna Zińczuk,1 Konrad Zaręba,2 Joanna Kamińska,1 Olga Martyna Koper-Lenkiewicz,1 Violetta Dymicka-Piekarska,1 Anna Pryczynicz,3 Katarzyna Guzińska-Ustymowicz,3 Boguław Kędra,2 Joanna Matowicka-Karna,1 Małgorzata Żendzian-Piotrowska,4 Anna Zalewska,5 Mateusz Maciejczyk4 1Department of Clinical Laboratory Diagnostics, Medical University of Bialystok, Białystok, 15-269, Poland; 2 2nd Clinical Department of General and Gastroenterological Surgery, Medical University of Bialystok, Białystok, 15-276, Poland; 3Department of General Pathomorphology, Medical University of Bialystok, Białystok, 15-269, Poland; 4Department of Hygiene, Epidemiology and Ergonomics, Medical University of Bialystok, Białystok, 15-222, Poland; 5Independent Laboratory of Experimental Dentistry, Medical University of Bialystok, Białystok, 15-276, PolandCorrespondence: Justyna ZińczukDepartment of Clinical Laboratory Diagnostics, Medical University of Bialystok, Waszyngtona 15a St., Białystok, 15-269, PolandTel +48 85 8 31 87 16Email [email protected] MaciejczykDepartment of Hygiene, Epidemiology and Ergonomics, Medical University of Bialystok, Mickiewicza 2c St., Białystok, 15-222, PolandTel +48 85 748 55 85Email [email protected]: In this study, we evaluated the total antioxidant capacity, nitrosative stress, and protein/DNA oxidation and glycoxidation products in patients with colorectal cancer regarding histopathological parameters associated with the tumour microenvironment, such as inflammatory infiltration and tumour budding and compare all determined parameters between tumours located in the right and left side of the colon and normal mucosa.Patients and Methods: Ferric reducing antioxidant power (FRAP), nitrosative stress (myeloperoxidase (MPO), nitrogen oxide (NO), peroxynitrite, and nitrotyrosine), protein oxidation products (protein carbonyls (PC), total thiols, and ischemia modified albumin (IMA)), protein glycooxidation products (tryptophan, kynurenine, N-formylkynurenine, dityrosine, Amadori product, advanced glycation end products (AGE)) and 8-hydroxydeoxyguanosine (8-OHdG) were measured in homogenates from normal and cancerous tissue of 30 patients with colorectal cancer.Results: Levels of FRAP (p=0.0009), IMA (p=0.0002), kynurenine (p< 0.0001), N-formylkynurenine (p< 0.0001), dityrosine (p< 0.0001), Amadori products (p=0.0024), AGE (p< 0.0001), MPO (p< 0.0001), NO (p< 0.0001) and nitrotyrosine (p=0.0011) were increased, whereas PC (p=0.0004), tryptophan (p< 0.0001), 8-OHdG (p< 0.0001) and peroxynitrite (p=0.0003) were decreased in the left-side tumour compared to the right-side tumour and normal mucosa.Conclusion: Our results showed that colorectal cancer is related with disturbances in antioxidant defense and increased oxidative and nitrosative damages to proteins and DNA. These parameters may be useful for evaluation the progression and differentiation of the tumour location. We also demonstrated that redox indicators may depend on the histological type of the tumour and may influence tumour invasion depth, presence of lymph node and distant metastasis, vascular and neural invasion, inflammatory infiltration, and tumour budding, which are part of the tumour microenvironment.Keywords: oxidative stress, nitrosative stress, redox biomarkers, colorectal cancer

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