A Review of Proteomic Studies in Uterine Leiomyosarcoma: Biomarkers, Pathways, and Clinical Potential

Uterine leiomyosarcoma (uLMS) is a rare but highly aggressive mesenchymal malignancy of smooth-muscle origin that represents a significant therapeutic challenge due to its poor prognosis and limited treatment options. Despite advances in molecular characterization, diagnosis remains difficult, and systemic therapies have shown limited success, contributing to a high recurrence rate and poor survival. Recent proteomic investigations have provided new insights into uLMS biology by exploring the global protein expression patterns that define malignant transformation and progression. Using high-resolution mass spectrometry (MS)-based techniques, quantitative proteomics, and integrated multi-omics approaches, researchers have begun to identify dysregulated proteins, signaling pathways, and post-translational modifications (PTMs) linked to tumor metabolism, extracellular matrix (ECM) remodeling, cell-cycle regulation, and chemoresistance. These studies have also uncovered candidate biomarkers that may improve the discrimination of uLMS from benign leiomyoma and have proposed novel therapeutic targets associated with metabolic reprogramming, kinase activation and tumor microenvironment (TME) modulation. This review summarizes recent advancements in uLMS proteomics, discusses their methodological underpinnings, highlights key molecular mechanisms and biomarkers, and explores their translational potential. Finally, we outline current limitations and future directions toward clinical implementation of proteomic findings in precision oncology for uLMS patients.