Abstract
Endometrial cancer (ECs) stands as one of the three major malignancies impacting females globally, with its incidence steadily increasing. ECs can be categorized into two types based on their clinicopathological features. Type I ECs typically exhibit low stage, favorable histological types, and low histological grade, correlating with a more favorable prognosis. Conversely, Type II ECs present with advanced-stage disease, aggressive behavior, and poorer histological types, resulting in a worse prognosis. The expression level of progesterone receptors (PR) holds significant importance in determining the prognosis of patients with ECs. Elevated levels of PR are linked to a more favorable prognosis, primarily attributed to progesterone's inhibitory influence on cancer cell proliferation and invasion. Moreover, progesterone promotes cell cycle inhibition through its regulation of PR, further contributing to improved outcomes in ECs. Nicalin (NCLN) plays a crucial role in facilitating the translocation of multichannel membrane proteins to the endoplasmic reticulum membrane and is implicated in embryonic development. Structurally akin to NODAL Modulator (NOMO), NCLN antagonizes NOMO during embryogenesis, forming a complex that antagonizes the Nodal pathway, thereby influencing mesoderm development. However, the precise relationship between NCLN and ECs remains incompletely understood. Our research findings reveal that NCLN actively stimulates the proliferation of ECs cells and exhibits a positive correlation with PR, albeit without impacting ER. Moreover, the expression levels of NCLN in ECs demonstrate associations with distinct histological types. These observations suggest that NCLN could emerge as a promising marker in the histological classification of ECs.