Development and Validation of a Novel Diagnostic Model for Childhood Autism Spectrum Disorder Based on Ferroptosis-Related Genes

Abstract

Autism spectrum disorder (ASD) is a highly genetic heterogeneous neurodevelopmental disorder, which is usually considered a heritable and heterogeneous neurodevelopmental disorder and has caused a great burden to society and families. Emerging roles of ferroptosis have been observed in neurological disorders. This study aimed to construct a diagnostic model based on ferroptosis-related genes (FRGs) to contribute to the early and precise diagnosis of childhood ASD. In the candidate FRGs, we identified 27 differentially expressed genes (DEGs) between ASD patients and typically developing (TD) controls. Four key FRGs were identified using the random forest analysis for further analysis. Utilization of the four gene expression, we constructed a diagnostic model and the AUC value in the training dataset (GSE18123) is 0.7002. We deem that a patient with a score less than 0.9904 is likely to have ASD. Three validation datasets (GSE111176, GSE113834, and GSE28521) were collected and the AUC value is 0.7442, 0.7444, and 0.6474, respectively. A multi-factor regulatory network based on four FRGs indicated that RORA, EAF1, NFYB, miR-4703-3p, and miR-6073 may play a role in the development of ASD. In addition, we found piperaquine may have the potential to be a promising drug for the treatment of ASD. Overall, we constructed a diagnostic model of childhood ASD, which could contribute to the precision diagnosis and timely treatment of childhood ASD.

Seleno-Metabolites and Their Precursors: A New Dawn for Several Illnesses?

“…This is an iron-dependent cell death involved in the pathology of numerous neurodegenerative pathologies, such as autism spectrum disorder (ASD) and spinal cord injury (SCI) [104][105][106][107][108][109][110][111]. ASD is complex neuropathology that involves a great number of heterogeneous neurodevelopmental impairments [112,113]. Despite the increased prevalence of ASD worldwide, few efficacious drugs are available for the treatment of this disease [109].…”

Insights on dental care management and prevention in children with autism spectrum disorder (ASD). What is new?

“…For example, the genetics of ferroptosis has been suggested as a possible methodology to diagnose autism very early. At least four ferroptosis-related genes (FRGs) have been linked with the likelihood, in the AUC (Area Under the Curve) values of ROC (Receiver Operating Characteristic) curves, of developing autism, particularly if involving the regulatory genes RORA (Related Orphan Receptor A), FAF1 (Fas-associated Factor 1), the microRNA gene miR-4703-3p, NFYB (Nuclear Transcription Factor Y Subunit Beta) and the microRNA miR-6073 ( 74 ). Nevertheless, genetics is not so routinely available, whereas neuroimaging might be much more affordable and available ( 75 ) and early motor signs ( 76 ).…”

Identification of Ferroptosis-Related Molecular Clusters and Immune Characterization in Autism Spectrum Disorder

“…In addition, suppressing GSH and GPX4 expression levels is usually accompanied by the accumulation of Fe 2+ and the activation of lipid peroxidation in Alzheimer’s disease (AD) ( Raven et al, 2013 ). A recent study has identified four key ferroptosis-related genes (FRGs) and constructed a diagnostic model for ASD based on these FRGs ( Wu X. et al, 2022 ). In addition, another study found that selenium could enhance autism-relevant behaviors and constrain ASD mouse induced ferroptosis ( Wu H. et al, 2022 ).…”