Oxidative Stress as a Biomarker for Predicting the Prognosis of Patients with Colorectal Cancer

Abstract

Introduction Excess oxidative stress is generated by inflammation and cancer, and it is involved in the development and metastasis of colorectal cancer. However, there are few reports on the relationship between blood oxidative stress and prognosis. This study examined the usefulness of derivatives of reactive oxygen metabolites (d-ROMs), a measure of oxidative stress, and the neutrophil-to-lymphocyte ratio (NLR), an inflammatory marker, as prognostic markers in colorectal cancer. Methods The study enrolled 163 patients who underwent colorectal cancer resection at our institution between 2013 and 2018. Blood samples were taken preoperatively to measure d-ROMs and NLR. Spearman’s correlation analysis was used to examine the relationships between d-ROMs and NLR, and Cox regression analysis was performed to identify factors associated with d-ROMs and NLR. The Kaplan–Meier method was used to calculate disease-specific survival (DSS). Results There was no correlation between d-ROMs and NLR. Tumor size was significantly associated with d-ROMs and NLR. DSS was significantly worse among patients with high d-ROMs or high NLR, although patients with high d-ROMs and high NLR had the worst DSS. In the multivariate analysis, distant metastasis and the high d-ROM/NLR combination were significant factors associated with DSS (P < 0.001, hazard ratio [HR] = 22.880 and P = 0.049, HR = 2.391, respectively). Conclusion Preoperative d-ROMs and NLR reflect the tumor size among patients with colorectal cancer. The combination of d-ROMs and NLR may effectively predict prognosis in patients with colorectal cancer.

Monitoring Metastatic Colorectal Cancer Progression According to Reactive Oxygen Metabolite Derivative Levels

“…Colon tissues are constantly exposed to intrinsic and extrinsic oxidative stress, which can promote carcinogenesis through protein denaturation, DNA damage, and lipid oxidation, promoting tumor growth, invasion, and metastasis through various metabolites [27][28][29][30]. Blood oxidative stress levels are higher in patients with colorectal cancer than in healthy individuals [15,31,32], and they show a strong association with tumor size, progression, and prognosis [16,18,22,32].…”

“…Quantitative methods for measuring stable oxidative stress in blood, such as via reactive oxygen metabolite derivative (d-ROM) measurement, have recently been developed [21]. Blood d-ROM levels tend to increase with tumor size and progression, and patients with high blood d-ROM levels have been associated with poor disease prognosis [16,18,22]. However, the effect of anticancer treatment on d-ROM levels in colorectal cancer is unclear.…”

Oxidative Stress, Inflammation and Colorectal Cancer: An Overview

“…The study suggests that oxidative stress contributes significantly to premature mortality in CRC patients. Work by Sawai et al [ 133 ] focused on the correlation of d-ROM and the neutrophil-to-lymphocyte ratio (NLR), an inflammatory marker, as possible prognostic markers. The results obtained during the period 2013–2018 indicate that CRC patients (n = 163) with high d-ROM and high NLR had the worst disease-specific survival.…”

Prognostic value of oxidative stress-related genes in colorectal cancer and its correlation with tumor immunity

“…The counteractive effects of ROS, such as ROS favoring the proliferation of cancer cells or causing cancer cell death due to excessive ROS production, have been noted, suggesting the tumor-suppressing or tumor-promoting role of ROS in cancer development [ 8 ]. Indexes related to OS are clinically useful in the prognosis evaluation of CRC patients [ 9 , 10 ]. Moreover, multiple studies have demonstrated the many OS-related genes are potential prognostic biomarkers in cancer treatment [ 11 – 13 ].…”