Low expression of SOD and PRX4 as indicators of poor prognosis and systemic inflammation in colorectal cancer

Sanghyun An¹Hye Youn Kwon¹Kwangmin Kim²SOOKI KIM³Cheol Su Kim³Bora Kim⁴Hyejin Do⁵Youngwan Kim^1,6*

• ¹Department of Surgery, Yonsei University Wonju College of Medicine, Wonju, Korea, Wonju, Gangwon, Republic of Korea
• ²Health Check-up Center, Wonju Severance Christian Hospital, Wonju, South Korea, Wonju, Republic of Korea
• ³Department of Microbiology, Yonsei University Wonju College of Medicine, South Wonju, Wonju, Republic of Korea
• ⁴Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, South Korea, Wonju, Republic of Korea
• ⁵Department of Anesthesiology, Chungju Medical Center, Chungju, South Korea, Chungju, Republic of Korea
• ⁶Graduate Medical Education, BayCare Health System 6901 Simmons Loop, Florida, United States

Objectives: Oxidative stress, characterized by an imbalance between the levels of reactive oxygen species (ROS) and antioxidants, plays a critical role in cancer progression. However, the prognostic significance of antioxidant markers in colorectal cancer (CRC) remains unclear. This study aimed to evaluate the expression of antioxidant markers in tumor tissues and investigate their association with clinicopathological features, survival, and systemic inflammation. Methods: We retrospectively analyzed 70 patients with CRC who underwent curative surgical resection. The tissue levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), peroxiredoxin 4 (PRX4), and thioredoxin (Trx) were measured in freshly frozen tissues, and the patients were classified into high and low expression groups using the 1st quartile as the cutoff. Associations between antioxidant levels in tumor tissue using ELISA and clinicopathological characteristics, laboratory inflammatory markers, and survival outcomes were analyzed. Results: Low SOD expression was significantly associated with a higher incidence of distant metastases. Similarly, low PRX4 expression was correlated with more aggressive tumor characteristics, including higher rates of distant metastasis, poor differentiation, and advanced T4 stage. Moreover, low PRX4 levels were linked to systemic inflammation, as reflected by increased neutrophil counts and neutrophil-lymphocyte ratio. Although not statistically significant, the low SOD and PRX4 groups exhibited worse 5-year disease-free survival. Conclusions: Low SOD and PRX4 expression was associated with aggressive tumor features, poor survival, and heightened systemic inflammation in patients with CRC. Given their association with tumor aggressiveness and systemic inflammation, antioxidant markers such as SOD and PRX4 may serve as supportive prognostic biomarkers to help identify patients at risk of adverse clinical outcomes in CRC.