Unveiling Racial Disparities in Localized Prostate Cancer: A Systems-Level Exploration of the lncRNA Landscape

Background/Objectives: Prostate cancer (PC) is the most common non-cutaneous cancer in men globally, with significant racial disparities. Men of African descent (AF) are more likely to develop PC and face higher mortality compared to men of European descent (EU). The biological mechanisms underlying these differences remain unclear. Long non-coding RNAs (lncRNAs), recognized as key regulators of gene expression and immune processes, have emerged as potential contributors to these disparities. This study aimed to investigate the regulatory role of lncRNAs in localized PC in AF men relative to EUs and assess their involvement in immune response and inflammation. Methods: A systems biology approach was employed to analyze differentially expressed (DE) lncRNAs and their roles in prostate cancer (PC). Immune-related pathways were investigated through over-representation analysis of lncRNA-mRNA networks. The study also examined the effects of vitamin D supplementation on lncRNA expression in African descent (AF) PC patients, highlighting potential regulatory roles in immune response and inflammation. Results: Key lncRNAs specific to AF men were identified, with several implicated in immune response and inflammatory processes. Notably, 10 out of the top 11 ranked lncRNAs demonstrated strong interactions with immune-related genes. Pathway analysis revealed their regulatory influence on Antigen Processing and Presentation, Chemokine Signaling, and Ribosome pathways, suggesting critical roles in immune regulation. Conclusions: These findings highlight the pivotal role of lncRNAs in PC racial disparities, particularly through immune modulation. The identified lncRNAs may serve as potential biomarkers or therapeutic targets to address racial disparities in PC outcomes.