Regional Proteomic Characterization of Uterine Leiomyomas: Implications for Molecular Pathways and Tumor Biology.

Abstract

Uterine leiomyomas are the most common benign smooth muscle tumors in women of reproductive age. Recent technological advances have enhanced the potential of proteomic studies to identify proteins and related signaling pathways involved in leiomyoma pathogenesis. This study performed comprehensive proteomic analyses of three leiomyoma subtypes, classified by their localizations, to provide new insights and a valuable resource for further studies. Tissue samples from both leiomyoma and normal myometrial tissues were collected from individuals undergoing hysterectomy for symptomatic leiomyomas. Proteins were extracted from tissue samples, enzymatically digested to generate peptides, and subsequently analyzed using high-resolution mass spectrometry (HR-MS). Biological significance and related pathways of differentially expressed proteins were revealed by Gene Ontology (GO) analyses. MS analyses revealed significant expression changes in 143, 152 and 146 proteins in submucosal, subserosal and intramural myomas, respectively. Top enriched categories of dysregulated proteins included RNA binding, oxidoreductase activity, cytoskeletal structural components, glutathione transferase activity, extracellular matrix organization, innate immunity, post-translational phosphorylation. The classification of differentially expressed proteins (DEPs) also highlighted the metabolite interconversion enzyme family in all three groups. Hydrolase, oxidoreductase and transferase subfamilies were common to all three groups, while isomerase, ligase and lyase subfamilies were present in the subserosal and intramural groups. Proteomic analyses provided important information about the dysregulated proteins in uterine leiomyomas and revealed various pathways to which they are related. The findings emphasize the need for further research, especially on the effects of oxidative stress on the immune response against tumor cells, the role of extracellular matrix proteins and enzymes in metabolic pathways.