Identification of immune-related biomarkers in embryos with neural tube defects via a bioinformatics analysis

Abstract

Background Neural tube defects (NTDs) are one of the most common types of birth defects. Oral folic acid (FA) prophylaxis is currently available, but the pathogenesis of NTDs is not fully understood. We conducted this study to examine the role of the immune landscape of NTDs and identify novel diagnostic and therapeutic biomarkers. Methods We downloaded the GSE33111 data set of 12 NTD embryos and 12 healthy embryos in the same period of fetal development from the Gene Expression Omnibus (GEO) database. We compared the healthy embryos and NTD embryos to identify the differentially expressed genes (DEGs). We also performed a functional enrichment analysis of the DEGs using the clusterProfiler package. We extracted the top 10 ranked genes as hub immune-related biomarkers. We then used receiver operating characteristic (ROC) curves to determine the expression levels of the hub immune-related genes and the accuracy of the diagnosis of NTDs. Finally, we analyzed the immune landscape of the NTD embryos and healthy embryos via a single-sample gene set enrichment analysis (ssGSEA). Results A total of 611 DEGs were identified by the differential analysis, including 95 immune genes. The functional enrichment analysis indicated that Epstein-Barr virus infection, antigen processing and presentation, inflammatory bowel disease, and type I diabetes mellitus were associated with NTDs. The results of the expression level analysis showed that the hub immune-related genes were more highly expressed in the NTD embryos than the healthy embryos. Additionally, the ROC curve analysis also indicated that the expression levels of the 10 hub immune-related genes were highly accurate in the diagnosis of NTDs [area under the curve (AUC) range, 0.708–0.812]. The immune infiltration analysis demonstrated that 20 of the 28 immune cell types were more highly infiltrated in the NTD embryos than the healthy embryos. Conclusions Immune-related genes are important regulators of the occurrence and development of NTDs.

Spina Bifida Prevention: A Narrative Review of Folic Acid Supplements for Childbearing Age Women

“…Most of the neural axis anomalies occur in the caudal spinal or cranial areas [2,3]. With an incidence of 0.1% in the Western world and 1.86% worldwide, there are approximately 300,000 cases of NTDs that occur annually [4][5][6], with 88,000 deaths occurring per year worldwide [7].…”

“…Genetics and environmental factors have significant contributing roles in the etiology of NTDs [2,4,5,7,8]. Genetics is implicated as a causative factor in 20% of the cases, whereas the nongenetic elements account for 80% of NTD incidence [9].…”

“…The prevention of NTDs by administration of folic acid has been studied and discussed in the literature [2,4,5,7,8,14]. On an international level, at least 400 μg of folic acid has been recommended in the first month before conception and throughout the first trimester [15,16].…”

Characterizing neuroinflammation and identifying prenatal diagnostic markers for neural tube defects through integrated multi-omics analysis

“…Prolonged neuroinflammation is believed to be associated with many neurological disorders, including Parkinson's disease [8], Alzheimer's disease [9], and multiple sclerosis [10]. A recent study has identified a series of immune-related genes in human NTDs [11]. Similarly, upregulated inflammation-related processes were found in spinal cords from rats with NTDs [12].…”

“…Current diagnostic modalities, such as maternal serum alpha-fetoprotein screening, fetal ultrasonography, and amniocentesis, have limitations in terms of sensitivity, specificity, and invasiveness [21][22][23]. A recent study has identified immune-related genes as diagnostic biomarkers of NTDs in fetal tissues [11]. However, these biomarkers lack practical application because the detection of fetal tissue during pregnancy is challenging and carries risks.…”