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Gene expression data of NMDAR-E Associated with Ovarian Teratoma

ABSTRACT: Gene expression data of NMDAR-E Associated with Ovarian Teratoma

PROVIDER: PRJNA1163713 | ENA |

REPOSITORIES: ENA

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Gene expression data of NMDAR-E Associated with Ovarian Teratoma

Project description:Purpose: To identify significantly differentially expressed genes and to investigate the intricate molecular regulatory network underlying anti-NMDA receptor encephalitis associated with ovarian teratoma. Methods: This retrospective study analyzed ovarian teratoma samples from patients with and without NMDAR-E. We employed RNA sequencing for gene expression profiling. qPCR and Western blotting were used for gene and protein expression validation. Results: We identified 2524 significantly differentially expressed genes. The changes were notable in mRNA levels in ovarian teratomas associated with NMDAR-E. Functional enrichment analysis highlighted 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.Conclusions: Our findings offer deeper insights into the pathophysiology of NMDAR-encephalitis associated with ovarian teratomas. The identified biomarkers, particularly in ferroptosis and immune activation pathways, provide potential targets for diagnosis and treatment.

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Evidence for antibody-mediated pathogenesis in anti-NMDAR encephalitis associated with ovarian teratoma.

Project description:We report the immunopathological analysis of the brain and tumor of two patients who died of anti-NMDAR-associated encephalitis, and of the tumor of nine patients who recovered. Findings included prominent microgliosis and deposits of IgG with rare inflammatory infiltrates in the hippocampus, forebrain, basal ganglia, and spinal cord. Detection of cells expressing markers of cytotoxicity (TIA, granzyme B, perforin and Fas/Fas ligand) was extremely uncommon. All tumors showed NMDAR-expressing neurons and inflammatory infiltrates. All patients’ NMDAR antibodies were IgG1, IgG2, or IgG3. No complement deposits were observed in any of the central nervous system regions examined. Overall, these findings coupled with recently reported in vitro data showing that antibodies downregulate the levels of NMDA receptors suggest that the antibody immune-response is more relevant than cytotoxic T-cell mechanisms in the pathogenesis of anti-NMDAR-associated encephalitis.

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Project description:Ovarian immature teratoma (IM) is a type of germinal malignant tumor, affecting children, adolescents and young adults. Event-free survival is below 25% in high-grade IM. Pediatric IM is rare and seldom studied, raising controversial issues such as histopathological standard and lack of specific biomarkers. This study aimed to perform microRNA (miRNA) microarray and identify specific differentially expressed miRNAs in IMs than in other types of ovarian tumors. Our work enables practitioners to optimally exploit relevant characteristics for precise diagnostic and therapeutic strategies in IM.

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GKAP acts as a genetic modulator of NMDAR signaling to govern tumor invasiveness

Project description:Genetic linkage analysis suggested that GKAP, a scaffold protein of the NMDA receptor (NMDAR), was a potential modifier of invasion in a mouse model of pancreatic neuroendocrine cancer (PanNET). Here we establish that GKAP governs invasive growth and treatment response of PanNET via its pivotal role in regulating the NMDAR pathway activity. Combining genetic knockdown of GKAP and pharmacological inhibition of NMDAR, we distilled gene expression signatures orchestrated by the NMDAR-GKAP axis, in addition to identifying two downstream effectors FMRP and HSF-1. Additionally, GKAP, FMRP, and HSF1 are functionally implicated in invasiveness of pancreatic ductal adenocarcinoma. Finally, gene expression signatures in tumors with low NMDAR activity are significantly associated with favorable patient prognosis in several cancer types.

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Project description:In germ cell tumors (GCT), a growing mature teratoma during or after chemotherapy with decreasing tumor markers is defined as ´growing teratoma syndrome` (GTS) according to its first describer Logothetis et al. in 1982. Due to the small number of available cases worldwide, not much is known about this continuously growing tumor and its pathogenesis. Especially in cases with extensive and surgical uncontrollable tumor mass, specific therapeutic options and biomarkers early indicating presence of GTS are still lacking. In this study, GTS was stratified into a slow (< 0.5 cm / month), medium (0.5 – 1.5 cm / month) and rapid (> 1.5 cm / month) group based on the tumor growth rate. We analyzed the secretome of 3 GTS samples of each subgroup and 3 teratomas. The secreted proteins were isolated from ex vivo cultivated tissues and analyzed by liquid-chromatography coupled to mass spectrometry (LS-MS).

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