Construction and validation of a histone-related gene signature for the diagnosis of endometriosis.

Objectives: Endometriosis is a common chronic disease in childbearing women and a major cause of infertility. Our study aimed to identify and validate a novel gene signature for diagnosing endometriosis based on histone-related genes (HRGs), and to investigate their biological functions in endometriosis.

Material and methods: RNA sequence data were downloaded from the Gene Expression Omnibus database, and HRGs were retrieved from the GeneCards database. We identified differentially expressed genes using the limma package, and constructed a diagnostic model using the rms package. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were performed for visualization, annotation, and integrated discovery. Subsequently, we validated the model using the recall and decision curve analysis (DCA). Additionally, we analyzed the immune microenvironment features using CIBERSORT.

Results: A total of 18 differentially expressed HRGs were identified in patients with endometriosis compared with controls. GO and KEGG enrichment was mainly in spindle organization, positive regulation of the cell cycle process, progesterone-mediated oocyte maturation, and cellular senescence and cell cycle. We obtained a signature of four HRGs (JUNB, FRY, LMNB1, and SPAG1). DCA revealed that the diagnostic model benefits patients with endometriosis, regardless of the incidence. CIBERSORT analysis showed that the number of plasma cells increased significantly in endometriosis samples from all four datasets.

Conclusions: Our findings provide novel insights into the function of HRGs in the development of endometriosis and identify a new signature of four HRGs that may serve as valuable diagnostic markers and therapeutic targets for this disease.