Integrated bulk and single-cell transcriptomic profiling reveals bromocriptine sensitivity genes and cellular targets in adenomyosis

Abstract

Objective: Bromocriptine has emerged as a potential treatment for adenomyosis. This study aimed to identify genes associated with Bromocriptine sensitivity and explore the biological processes and cell-type-specific expression patterns involved.

Methodology: A cross-sectional bioinformatics study was carried out at Shenzhen Baoan Shiyan People’s Hospital from August 2023 to January 2025. We performed differential expression analysis on endometrial RNA-seq data from patients with adenomyosis before and after Bromocriptine treatment. Functional enrichment analysis was conducted to identify pathways influenced by treatment. Candidate genes were validated in two datasets by comparing normal and adenomyotic endometrial tissues. Single-cell RNA sequencing analysis on eutopic, ectopic and control endometrial samples was conducted to further explore their cellular and molecular regulation pathways.

Results: Differential expression genes after Bromocriptine treatment, with enrichment in pathways such as hormone response, connective tissue development and extracellular matrix organization. Cross-validation with external datasets identified nine candidate genes as Bromocriptine sensitivity markers. Single-cell analysis revealed distinct cellular origins for these genes, with ADAM12 and HOXA11 enriched in smooth muscle and epithelial cells and SFRP1 and SESN3 predominantly expressed in fibroblasts. Notably, several genes showed increased expression in ectopic lesions, supporting their involvement in disease progression and treatment response.

Conclusion: Our integrative analysis identified key genes and pathways associated with Bromocriptine sensitivity in adenomyosis. These findings provide insights into the drug’s mechanism of action and highlight potential biomarkers and therapeutic targets.