Pro-Oxidant Enzymes, Redox Balance and Oxidative Damage to Proteins, Lipids and DNA in Colorectal Cancer Tissue. Is Oxidative Stress Dependent on Tumour Budding and Inflammatory Infiltration?

Justyna Zińczuk,Konrad Zaręba,Anna Zalewska,Joanna Kamińska,Bogusław Kędra,Mateusz Maciejczyk,Katarzyna Guzińska-Ustymowicz,Violetta Dymicka-Piekarska,Anna Pryczynicz,Olga Koper-Lenkiewicz,Joanna Matowicka-Karna

doi:10.3390/cancers12061636

Justyna Zińczuk, Konrad Zaręba + Show 9 more

Open Access

https://doi.org/10.3390/cancers12061636

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Journal: Cancers	Publication Date: Jun 20, 2020
Citations: 53	License type: CC BY 4.0

Affiliation: Medical University of Białystok

Abstract

This study is the first to assess redox homeostasis in patients with colorectal cancer (CRC) in respect to histopathological parameters associated with the tumour microenvironment such as tumour budding and inflammatory infiltration. Pro-oxidant enzymes (NADPH oxidase (NOX), xanthine oxidase (XO)), antioxidant barrier (Cu,Zn-superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), reduced glutathione (GSH)), redox status (total antioxidant (TAC)/oxidant status (TOS)) and oxidative damage products (advanced glycation end products (AGE), advanced oxidation protein products (AOPP), malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG)) were determined in both the normal and cancerous tissue of 29 CRC patients. The activity of NOX (p < 0.01) and XO (p = 0.01), as well as SOD (p < 0.0001), CAT (p < 0.0001) and TAC level (p < 0.01) were significantly higher in tumour tissue than in normal colon mucosa. Oxidative damage products (AGE—p < 0.01, AOPP—p < 0.001, MDA—p < 0.001, 8-OHdG—p < 0.0001) were also higher in cancerous colon tissue. Furthermore, we observed that CAT (p < 0.05) and XO (p < 0.05) activity depends on the intensity of inflammatory infiltration. Oxidative stress index (OSI) (p < 0.05) and MDA (p < 0.01) values were significantly higher in patients with tumour budding (TB) > 5 versus cases with TB < 5. However, OSI level did not differ significantly between cancer and normal tissue. Our results confirm that CRC is associated with enzymatic/non-enzymatic redox imbalance and increased oxidative damage to proteins, lipids and DNA. The determination of these biomarkers could be useful for the evaluation of the tumour progression.

Highlights

Colorectal cancer (CRC) is one of the cancers with the highest dynamics of incidence in the world.According to GLOBOCAN database from 2018, colorectal cancer was classified as third most common type of cancer in the world among men and second most frequent one in women
The aim of our study was to evaluate the redox status, enzymatic and non-enzymatic antioxidants as well as oxidative damage to proteins, lipids and DNA in tumour tissue compared to normal adjacent mucosa in colorectal cancer patients
Over 65% patients had a pT2 stage of tumour which had grown through the muscularis propria and into the subserosa as well as into tissues surrounding the colon

Summary

Introduction

Colorectal cancer (CRC) is one of the cancers with the highest dynamics of incidence in the world.According to GLOBOCAN database from 2018, colorectal cancer was classified as third most common type of cancer in the world among men and second most frequent one in women. CRC is responsible for 9.2% of all cancer deaths, which places it second in terms of mortality among all cancers [1]. Despite screening tests, such as colonoscopy and faecal occult blood tests, about 20–25%. In order to improve such unfavourable statistics, it is crucial to understand the mechanisms involved in CRC carcinogenesis. It may facilitate the early detection of cancer, prevent its progression into an advanced stage, and enable the application of treatment which would significantly reduce CRC mortality

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