Abstract
Background: Uterine sarcoma (US) is an extremely rare and aggressive gynecologic malignancy with a poor overall survival (OS). The early screening and diagnosis of uterine sarcoma is still challenging, while efficient prognostic biomarker is currently lacking. In this study, we evaluated the expression of β-catenin in different US subtypes and the relationship between survival and clinicopathological characteristics by comparative analyses, then explored potential molecular mechanisms.
Methods: We evaluated the expression of β-catenin in different US subtypes and the relationship between survival and clinicopathological characteristics by comparative analyses. Utilizing a Sweden microarray dataset (GSE119043, n=50) and a Suining clinical cohort (n=31), we analyzed β-catenin expression profiles and corresponding clinicopathological characteristics. To assess the expression level of β-catenin in US subtypes, we conducted immunohistochemistry (IHC). Survival analysis was used to assess the relationship between β-catenin expression and prognosis in US patients. Gene set enrichment analysis (GSEA) was performed to characterize the specific pathways involved in the β-catenin expression.
Results: Immunohistochemistry indicated that the expression level of β-catenin significantly upregulated in the uterine sarcoma (US) group compared to both the normal uterine smooth muscle (UNSM) and uterine leiomyoma (ULM) groups (P<0.05). IHC also exhibited a significant difference in β-catenin expression levels in four pathological subtypes. Leiomyosarcoma (LMS) and high-grade endometrial stromal sarcoma (HG-ESS) suggested higher levels of β-catenin expression compared with adenosarcoma (AS) or low-grade endometrial stromal sarcoma (LG-ESS), but no statistically significant difference was found in box plot. Survival analysis showed that no significance between β-catenin expression levels and survival. Only tumor recurrence was significantly correlated with poor survival. Tumor type, lymphadenectomy, family history of malignancy and tumor recurrence remained significant predictors of overall survival (OS), while only tumor stage and tumor recurrence had prognostic significance for progression-free survival (PFS). Age, tumor size, menopausal status, CA125, adjuvant chemotherapy, and adjuvant radiotherapy, were not associated with survival (P>0.05). GSEA indicated that transcriptional misregulation in cancer, Wnt, AMPK, MAPK, PI3K, p53, Ras, and TNF signaling pathway were positively enriched in β-catenin high-expression group.
Conclusion: β-catenin was highly expressed in uterine sarcoma and promising as a novel potential biomarker for diagnosis and prognosis.