Abstract
Colorectal cancer (CRC) as one the most common cancer type is associated with oxidative stress. Surgery is the only curative modality for early-stage CRC. The aim of this study was to evaluate the oxidative damage biomarkers as well as enzymatic and nonenzymatic antioxidants in patients with CRC before and after tumor resection and in healthy controls. 60 patients with stage I/II colorectal adenocarcinoma and 43 healthy controls were recruited in this study. We measured plasma levels of oxidative damage biomarkers, including advanced oxidation protein products (AOPP), advanced glycation end products (AGEs), malondialdehyde (MDA), and oxidized low-density lipoprotein (ox-LDL) at baseline and after tumor removal. We also evaluated the plasma activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) as enzymatic antioxidants and the ferric reducing antioxidant power (FRAP) assay for nonenzymatic antioxidant capacity. Patients with CRC had significantly higher AGE, AOPP, MDA, and ox-LDL and also FRAP levels and higher SOD and GPx and lower CAT activity levels compared to healthy controls (p < 0.05). We did not observe any statistically significant correlation between redox biomarkers and the size and stage of the tumor. AGEs (72.49 ± 4.7 vs. 67.93 ± 8.8, p < 0.001), AOPP (137.64 ± 21.9 vs. 119.08 ± 33.1, p < 0.001), MDA (3.56 ± 0.30 vs. 3.05 ± 0.33, p < 0.001), and ox-LDL (19.78 ± 0.97 vs. 16.94 ± 1.02, p < 0.001) concentrations reduced significantly after tumor removal. The largest effect sizes were found in ox-LDL (d = −2.853, 95% CI 2.50-3.19) and MDA (d = −1.617, 95% CI 0.43-0.57). Serum FRAP levels (1097.5 ± 156.7 vs. 1239.3 ± 290, p < 0.001) and CAT (2.34 ± 0.34 vs. 2.63 ± 0.38, p < 0.001), GPx (102.37 ± 6.58 vs. 108.03 ± 6.95, p < 0.001), and SOD (5.13 ± 0.39 vs. 5.53 ± 0.31, p < 0.001) activity levels increased significantly after surgery. The largest effect sizes among antioxidants were seen in SOD (d = 1.135, 95% CI 0.46-0.34) and GPx (d = 0.836, 95% CI 0.35-0.23). This study indicated that patients with colorectal cancer had higher levels of oxidative stress and antioxidant activity compared to healthy controls. After surgical resection of tumor, we observed a substantial improvement in redox homeostasis.
Highlights
Colorectal cancer (CRC) is one of the most common malignant cancers and the second leading cause of cancer-related death worldwide [1]
Comparison of lipid peroxidation products, protein oxidation products (AOPP and advanced glycation end products (AGEs)), enzymatic antioxidants (SOD, glutathione peroxidase (GPx), and CAT), and antioxidant index (FRAP) in healthy controls and patients before and after surgery are displayed as bar charts in Figures 1 and 2
The antioxidant activity levels of GPx (102:37 ± 6:58 vs. 90:1 ± 7, p < 0:001) and superoxide dismutase (SOD) (5:13 ± 0:39 vs. 4:34 ± 0:35, p < 0:001) and antioxidant index of ferric reducing antioxidant power (FRAP) (1097:5 ± 156 vs. 1000 ± 213:9, p = 0:013) before surgery were significantly higher than control levels
Summary
Colorectal cancer (CRC) is one of the most common malignant cancers and the second leading cause of cancer-related death worldwide [1]. Nutritional oxidative stress and inflammation of the colonic mucosa play an essential role in the molecular mechanism of CRC [2]. High incidence of cancer in colorectal area, compared to other regions of the GI tract, may be explained by intracolonic free radical formation [3]. Considerable research is being done in redox and has revealed that the oxidative stress is closely related to all aspects of cancer, from carcinogenesis to tumor progression and from prevention to treatment. Cancer initiation and progression have been linked to oxidative stress by increasing DNA mutations or inducing DNA damage, genome instability, and cell proliferation [4,5,6].
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