Significance of 8-OHdG Expression as a Predictor of Survival in Colorectal Cancer

Abstract

Simple Summary Although oxidative stress regulates essential signaling pathways, oxidative DNA damage causes cancer initiation and progression. Given that the relationship between oxidative stress and colorectal cancer (CRC) remains poorly understood, we performed immunohistochemistry to detect 8-hydroxy-2 & PRIME; deoxyguanosine (8-OHdG) in 564 patients with CRC and conducted survival analysis based on the pathological stage to identify novel biomarkers. We found that low 8-OHdG levels were associated with a poor prognosis. Further, when 8-OHdG expression was combined with the tumor node metastasis stage, if 8-OHdG expression was low in the same stage, the prognosis was poor, suggesting that 8-OHdG may be an essential biomarker of CRC.Abstract The incidence of colorectal cancer (CRC) is increasing worldwide. 8-hydroxy-2 & PRIME;-deoxyguanosine (8-OHdG), one of the most prevalent DNA alterations, is known to be upregulated in several carcinomas; however, 8-OHdG has not been used to predict the prognosis of patients with CRC. We aimed to determine 8-OHdG levels in patients with CRC using immunohistochemistry and conducted a survival analysis according to the pathological stage. The 5-year event-free survival (EFS) and disease-specific survival (DSS) hazard ratios (HRs) of the low 8-OHdG subgroup were 1.41 (95% confidence interval (CI): 1.01-1.98, p = 0.04) and 1.60 (95% CI: 1.12-2.28, p = 0.01), respectively. When tumor node metastasis (TNM) staging and 8-OHdG expression were combined, the 5-year EFS and DSS HRs of patients with CRC with low 8-OHdG expression cancer at the same TNM stage (stage III/Ⅳ) were 1.51 (95% CI: 1.02-2.22, p = 0.04) and 1.64 (95% CI: 1.09-2.48, p = 0.02), respectively, compared to those with high 8-OHdG expression cancer, indicating a poor prognosis. Therefore, low 8-OHdG expression is a significant predictive factor for 5-year EFS and DSS in patients with CRC, and it can serve as an essential biomarker of CRC.