For a study, the aim was to find out what role increased CRABP2 expression plays in the development and progression of endometrial cancer (EC). Using a decision tree classifier, patients were divided into 2 groups using a decision tree classifier, those with high and those with low CRABP2 expression. In this study, the predictive and clinicopathological implications of elevated CRABP2 expression were analyzed using univariate and multivariate statistical methods. Differential expression analysis was used to create a “CRABP2 gene signature,” which was then examined using network-based methods. 

The results were confirmed in a new cohort of 120 endometrial tissues from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and in the Cancer Dependency Map (DepMap). High CRABP2 expression was found in only 60 (11%) TCGA patients, while low expression was found in 468 (89%) patients. Serous EC, shorter overall survival, higher stages, and higher grades were all linked to high expression. Expression of CRABP2 linked with downstream retinoic acid receptors (RARG and RARA) and was predictive of a poorer outcome in serous EC. ELP3 and BMP7 controlled the expression of the CRABP2 gene signature, which was enriched for Polycomb target gene sets. 

CRISPR-Cas9 screenings found associations between the cell-fitness score of BMP7 after gene deletion and CRABP2, and BMP7 expression was higher in the CRABP2-high group, which was associated with a poorer prognosis. The inverse was true for ELP3, indicating that the 2 master regulators have opposing effects. The presence of CRABP2 indicates advanced disease and a dismal outlook in EC. There is a negative correlation between RARA and RARG expression and CRABP2 and a poorer prognosis in more advanced histological subtypes. Functionally relevant mechanisms driving aberrant CRABP2 expression were discovered, including polycomb target gene sets and two master regulators, ELP3 and BMP7.