NUMB in Endometrial Pathology: From Adenomyosis Expression Patterns to Endometrial Cancer Survival Implications

Adenomyosis, a prevalent gynecologic condition involving invasion of endometrial tissue into the myometrium, remains poorly understood in terms of its molecular pathogenesis. Numb, an important regulator of cellular destiny and stem cell maintenance, has been implicated in numerous proliferative diseases; however, the role for Numb in adenomyosis has not yet been investigated. This research examines the degree to which Numb protein may play a role in the pathogenesis of adenomyosis and additional invasive endometrial diseases. This study analyzed Numb protein expression in tissues from 21 adenomyosis patients and 14 controls using immunohistochemistry. Numb levels were evaluated in eutopic endometrium, ectopic lesions, and myometrium. Additionally, comprehensive bioinformatics analyses were performed including TCGA expression analysis, STRING protein-protein interaction network analysis, and Kaplan-Meier survival analysis to elucidate the clinical significance and mechanistic role of NUMB in endometrial pathology linked to invasive growth. Compared to controls (p < 0.001), adenomyosis patients' eutopic endometrium and myometrium showed considerably higher levels of numb expression. It was predominantly observed in single cells rather than clusters. No significant variation was noted across menstrual cycle phases. Elevated Numb levels in the myometrium suggest a potential role in tissue invasion. TCGA analysis revealed significant associations between NUMB alterations and expression patterns in endometrial carcinoma, with copy number alterations showing a dose-dependent relationship with the expression levels. STRING network analysis identified NUMB as a central hub protein with 20 high-confidence interactions, particularly enriched in Notch signaling pathway components (FDR = 1.0 × 10^-15). Kaplan-Meier survival analysis demonstrated that endometrial carcinoma patients with NUMB alterations had significantly better overall survival compared to unaltered cases (p = 9.119 × 10^-3), with 92% vs. 73% survival at 100 months. This study presents new evidence of elevated Numb expression in adenomyosis, suggesting that it may play a part in the pathophysiology of the disease and that it is a useful marker for dysregulation of endometrial stem cells. The comprehensive bioinformatics analyses establish NUMB as a central regulator of endometrial homeostasis with significant prognostic value in endometrial malignancies, providing mechanistic insights into the pathogenesis of invasive endometrial diseases and identifying potential therapeutic targets.