Deciphering the molecular landscape of NMDAR-E associated ovarian teratomas: a Multi-Omics approach

Anti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E) is an autoimmune disorder often associated with ovarian teratomas. It involves antibodies against the neuronal NMDAr1 subunits of NR1, but the pathogenesis and molecular mechanisms are not fully understood. To identify significantly differentially expressed genes and proteins and investigate the intricate molecular regulatory network underlying anti-NMDA receptor encephalitis (NMDAR-E) associated with ovarian teratomas. This retrospective study analyzed ovarian teratoma samples from patients with and without NMDAR-E. RNA sequencing and iTRAQ coupled LC-MS/MS analysis were used for gene and protein expression profiling. qPCR and western blotting were used to validate the gene and protein expression. We identified 2524 significantly differentially expressed genes and 34 proteins. The changes were notable at the mRNA and protein levels in ovarian teratomas associated with NMDAR-E. Functional enrichment analysis highlighted the extracellular matrix and immune activation pathways. Key genes and proteins involved in ferroptosis and immune activation, including SLC40A1, GGH, FKBP11, CCDC80, and ANK3, showed significant expression differences. Our findings provide preliminary insights into the pathophysiology of NMDAR-E associated with ovarian teratomas. These results may generate hypotheses for future mechanistic studies, and the candidate biomarkers identified warrant further validation before clinical translation.