Construction of a Diagnostic Model and a lncRNA-Associated ceRNA Network Based on Apoptosis-Related Genes for Schizophrenia

Abstract

Background and Aim. Schizophrenia is a complex psychiatric disorder with an unknown etiology. Previous studies suggest that apoptosis is potentially involved in the pathophysiology of schizophrenia, but whether apoptotic markers can help diagnosis of schizophrenia has not been reported. This study aimed to establish a potential diagnostic model based on apoptosis-related gene expression in blood samples and to construct a competing endogenous RNA (ceRNA) network that could provide mechanistic insight of schizophrenia. Methods. Gene expression profiles and apoptosis-related data were downloaded from the Gene Expression Omnibus and Molecular Signature databases, respectively. Apoptosis-related differentially expressed mRNAs (DEGs) and miRNAs (DEMs) from blood samples between the schizophrenia and healthy control individuals were screened. A diagnostic model was developed using the data from univariate and least absolute shrinkage and selection operator (LASSO) regression analyses, followed by validation using the GSE38485 dataset. Cases were divided into low-risk (LR) and high-risk (HR) groups based on the risk score of the model, and differences in immune gene sets and pathways between these two groups were compared. Finally, a ceRNA network was constructed by integrating long non-coding RNAs (lncRNAs), DEMs, and DEGs. Results. A diagnostic model containing 15 apoptosis-related genes was developed and its diagnostic efficiency was found to be robust. The HR group was correlated with higher immune scores of chemokines, cytokines, and interleukins; it was also significantly involved in pathways such as pancreatic beta cells and early estrogen response. A ceRNA network composed of 2 lncRNAs, 14 miRNAs, and 5 mRNAs was established. Conclusions. The established model is a potential tool to improve the diagnostic efficiency of patients with schizophrenia, and the nodes included in the ceRNA network might serve as biomarkers and therapeutic targets for schizophrenia.