Single-Nuclei RNA Sequencing Reveals Obesity-Driven Reprogramming of Estrogen Signaling in Endometrioid Adenocarcinoma

To address this, we performed single-nuclei RNA sequencing on thirteen primary tumors from postmenopausal patients with normal and obese body mass indices. Tumors from obese patients exhibited widespread transcriptional remodeling across tumor and immune compartments.

Notably, weighted gene correlation network analysis revealed that estrogen receptor–associated gene modules in tumors from obese patients were compositionally distinct from those in normal-weight patients, suggesting that estrogen may signal through alternative regulatory networks in the obese tumor microenvironment. Additional obesity-associated features included epithelial-to-mesenchymal transition, metabolic stress, immune suppression, and altered cell–cell communication.