The role of oxidative stress, tumor and inflammatory markers in colorectal cancer patients: A one-year follow-up study

Abstract

Oxidative stress (OS) and inflammation are known to play an important role in colorectal cancer (CRC). This study analyzed tumor, inflammatory and OS markers in CRC patients and in a control group. In addition, the evolution of these markers was evaluated after one-year of follow-up treatment. This was a longitudinal and prospective, observational study in 80 CRC patients who were candidates for tumor resection surgery and/or chemo-radiotherapy treatment and a healthy control group (n = 60). Subsequently, catalase (CAT), reduced glutathione (GSH), oxidized glutathione (GSSG) and GSSG/GSH ratio in serum and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and F2-IsoProstanes (F2-IsoPs) in urine at 1, 6 and 12 months after treatment was analyzed. Tumor markers (CEA and CA 19.9), as well as inflammatory markers-leukocytes, neutrophils, neutrophil/lymphocyte (N/L) index, platelets, fibrinogen, C-reactive protein (CRP), and interleukin 6 (IL6)- were also analyzed. As expected, levels of CEA and CA 19.9 and markers of inflammation, except CRP, were significantly higher in CRC compared to the control group. Regarding OS markers, a decrease in CAT and GSH and an increase in GSSG, GSSG/GSH ratio, 8-oxodG and F2-IsoPs were found in CRC patients compared to healthy controls at baseline. After treatment, an improvement of their inflammation profile was accompanied by a progressive recovery of antioxidant enzyme activities and the decline of oxidative byproducts both in serum and urine. Based on the results obtained, we propose the assay of urinary 8-oxodG and F2-IsoPs, as well as serum CAT, GSH, GSSG as a marker for the evaluation of OS and the clinical follow-up of CRC patients.

Keywords: 8-oxodG; Catalase; Colorectal cancer; F2-isoprotanes; Glutathione system; Oxidative stress.

Fig. 1

Flow chart of the CRC patients and healthy controls in the longitudinal study.

Fig. 2

Levels of tumor markers in controls and CRC patients. CEA: carcinoembryonic antigen; CA 19.9: carbohydrate antigen 19.9. Results expressed as mean ± standard error. The statistical differences when comparing patients follow-up times are indicated by the p in the upper margin and between each patient are indicated by letters, so that the means sharing these letters do not present statistically significant differences (p > 0.05). Differences between the control group and the different patient times are represented by *(p < 0.05) and **(p < 0.001).

Fig. 3

Levels of inflammatory markers in controls and CRC patients. N/L: neutrophil/lymphocyte index; IL-6: interleukin 6; CRP: C-reactive protein. Results expressed as mean ± standard error. The statistical differences when comparing patients follow-up times are indicated by the p in the upper margin and between each patient are indicated by letters, so that the means sharing these letters do not present statistically significant differences (p > 0.05). Differences between the control group and the different patient times are represented by *(p < 0.05) and **(p < 0.001).

Fig. 4

Levels of oxidative stress markers in controls and CRC patients. CAT: catalase; GSH: reduced glutathione; GSSG: oxidized glutathione; 8-oxodG: 8-oxo-7,8-dihydro 2′-deoxy-guanosine; F2-IsoPs: F2-Isoprostanes. Results expressed as mean ± standard error. The statistical differences when comparing patients follow-up times are indicated by the p in the upper margin and between each patient are indicated by letters, so that the means sharing these letters do not present statistically significant differences (p > 0.05). Differences between the control group and the different patient times are represented by *(p < 0.05) and **(p < 0.001).