Identifying A Relationship Between Oxidative Stress And Immune Infiltration In Prostate Cancer Patients With Health Disparities Using Prostate Tumor Microarrays

Prostate cancer (PCa) ranks as the second most diagnosed cancer in American men, with an estimated 288,300 cases and approximately 34,700 deaths in 2023. Our research aims to understand how PCa progresses and becomes aggressive to help lower these numbers. Reactive oxygen species (ROS) are known to cause molecular damage to their unstable oxygen molecules. Our lab’s studies indicate high oxidative stress (OS) biomarkers correspond with PCa progression recurrence. However, the sources of high ROS levels in PCa are still unclear. Immune infiltration, identified in PCa, plays a role in its pathophysiology yet the relationship between immune cells with ROS in PCa progression/aggression and their contribution to cancer health disparities remains understudied. We hypothesize that immune cell infiltration in PCa tissues generates ROS to address the knowledge gaps, leading to oxidative stress and the following PCa progression. Utilizing Aperio Image Scope, a pathology slide viewing software, to identify immune infiltration and to quantify ROS-induced oxidative stress markers in tumor microarray slides constructed from 152 cases of PCa patients and 32 cases of non-PCa patients. Remarkably, expression levels of two OS biomarkers, 4-hydroxy-2-nonenal adducted proteins (4HNE) and peroxiredoxin sulfonylation (PrxSO3), are significantly increased in PCa patients who have immune cell infiltration compared to PCa patients without immune cell infiltration (1.2-fold increases for both markers). Interestingly, the level of PrxSO3 is significantly higher in Caucasians than African American PCa patients (1.35-fold higher) while PCa patients who live in the Appalachia area showed a significantly higher level of 4HNE (1.35-fold increase), compared to non-Appalachians. Overall, our results suggest that: 1) the presence of immune cells in PCa tissues could be a cause of high OS in PCa patients and 2) H2O2 could be the mediator for oxidative stress-promoted PCa progression, as H2O2 production by immune cells leads to 4HNE and PrxSO3.