Deciphering the Pleiotropic Role of ARID1a and RIF1 in Endometrioid Ovarian Cancer.

Given the challenges in early detection and diagnosis, understanding the molecular underpinnings of endometrioid ovarian cancer (EOC) is crucial for improving patient outcomes. This multi-level study provides a new perspective on EOC, focusing on the expression of ARID1a (BAF250a) and RIF1. This study evaluates patient cohorts with EOC through semi-quantitative immunohistochemical staining of BAF250a (protein encoded by ARID1a) and RIF1 proteins alongside mutations that influence the gene expression of ARID1a and RIF1. Besides survival analyses, platinum- and taxane-based treatment responsiveness with regard to ARID1a and RIF1 expression has been analyzed using an online available database. Histological and immunohistochemical analysis of clinical samples revealed a significant reciprocal alteration in protein expression, characterized by a marked reduction in the tumor suppressor BAF250a (p < 0.0001) and a concomitant elevation of RIF1 (p < 0.0001) in EOC compared to controls. Tumors harboring mutations in BRCA1 exhibited significantly (p = 2.82 × 10-4) lower ARID1a expression levels compared with corresponding wild-type tumors, whereas LAMB3-mutant tumors showed a significant (p = 5.16 × 10-3) upregulation of RIF1 mRNA expression. In conclusion, our study offers a new perspective, emphasizing that EOC is a distinct clinical and molecular entity. We demonstrated the expression patterns of ARID1a/BAF250a and RIF1 in EOC, establishing their potential relevance in the context of tumor biology and malignant transformation.