28P - Xanthine oxidase as a prognostic factor in colorectal cancer metastatic disease

Background

Obesity and related diseases, namely, diabetes and metabolic syndrome, are associated with chronic inflammation and colorectal cancer (CRC). In CRC liver metastases (mCRC) and adjacent liver tissue defects are formed in the mitochondrial electron transport chain that causes mitochondrial dysfunction, activation of redox-molecules (SR, NO) generation sources and MMP-2, -9 activity. Radical oxygen species take a part in the regulation of gelatinases (MMP-2 and -9) and the xanthine/xanthine oxidase reaction is widely used as a source of exogenous ROS in considering of MMPs. The aim of the study was to determine the state of XO, SR and MMPs in liver tissue and CRC liver metastases (MT) and set the clinical significance of obtained results.

Methods

The prospective study on 37 mCRC patients who underwent the liver resection due metastatic disease has been performed. The rate of SR generation of neutrophils and in the tissue samples, the rate of XO and the activity of matrix metalloproteinases in the tissue samples was measured accordingly study design.

Results

The highest level of XO in mCRC patients was detected in metastatic tissue (1.47±0.18 a.u.). The level of XO enzyme in the adjacent tissue (AT) and distant tissue (DT) were 0.38±0.10 a.u. (p<0.05) and 0.19±0.008 a.u. (р<0,05) respectively. A correlation was found between the BMI and amount of XO in DT of the liver r² = 0,64. The total activity of gelatinases in subgroup of mCRC patients with BMI ≥ 25 was found to be significantly higher than in normal body weight patients withing the DT (1.52; p<0.001), as well as in the AT (1.28 times; p<0.001). High XO levels (HR (95% CI) = 0,002 (2,63 to 15.05) P = 0,002) and SR generation levels (HR (95% CI) = 0,01 (2,4 to 10,37) P = 0,01) in adjusted liver tissue to metastatic lesions had a negative impact on overall overall survival rates.

Conclusions

Xanthine oxidase and superoxide radicals can be a new metastatic disease prognostic factors for colorectal cancer patients, the latter requiring further randomized trials.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.