Oxidative Stress and Its Molecular Effectors in Uterine Smooth Muscle Tumors: Bridging Epigenetic Regulation and Glycoprotein Biomarkers

Background: Uterine smooth muscle tumors present a diverse clinical spectrum, ranging from ubiquitous benign leiomyomas to highly lethal uterine leiomyosarcomas (uLMSs). The preoperative differentiation of these entities, alongside the intermediate smooth muscle tumors of uncertain malignant potential (STUMP), remains an unresolved clinical challenge. Methods: This comprehensive review synthesizes the current literature on the pathogenesis of uterine smooth muscle tumors, focusing on the role of oxidative stress and its downstream molecular effectors. We evaluate the interplay between oxidative stress markers, epigenetic regulation via microRNAs (miRNAs), and circulating glycoproteins. Results: Increased oxidative stress is a hallmark associated with uLMS, characterized by altered antioxidant enzyme activity and elevated lipid peroxidation products such as malondialdehyde (MDA). This oxidative burden is associated with DNA damage and profound genomic instability, participating in the evolution of the malignant phenotype. Concurrently, the stressed tumor microenvironment exhibits significant epigenetic deregulation. Tumor-suppressive miRNAs (e.g., the miR-29 and miR-200 families) are downregulated, while oncogenic miRNAs (e.g., miR-21) are upregulated, promoting survival and proliferation pathways. Furthermore, galectin-1, a glycoprotein responsive to microenvironmental stress, is elevated in the serum of uLMS and STUMP patients, demonstrating high specificity in investigated cohorts, though limited sensitivity (47%), whereas mucin-1 (MUC1) shows no significant diagnostic utility. Conclusions: Oxidative stress is strongly associated with the genomic instability and molecular derangements observed in uterine sarcomas. Integrating oxidative stress indicators with specific miRNA signatures and galectin-1 levels could potentially yield robust, non-invasive diagnostic panels. However, prospective validation in large, independent cohorts is strictly required before these markers can be implemented to improve preoperative risk stratification and guide targeted therapeutic interventions.