Identification of a Hypoxia-Related Signature as Candidate Detector for Schizophrenia Based on Genome-Wide Gene Expression

Zhitao Li, Xinyu Sun, Jia He, Dongyan Kong, Jinyi Wang, Lili Wang

Schizophrenia (SCZ), a severe neuropsychiatric disorder with high genetic susceptibility, has high rates of misdiagnosis due to the unavoidably subjective factors and heterogeneous clinical presentations. Hypoxia has been identified as an importantly risk factor that participates in the development of SCZ. Therefore, development of a hypoxia-related biomarker for SCZ diagnosis is promising. Therefore, we dedicated to develop a biomarker that could contribute to distinguishing healthy controls and SCZ patients. GSE17612, GSE21935 and GSE53987 datasets, consist of 97 control samples and 99 SCZ samples, were involved in our study. The hypoxia score was calculated based on the single-sample gene-set enrichment analysis (ssGSEA) using the hypoxia-related differentially expressed genes to quantify the expression levels of these genes for each SCZ patients. Patients in high-score groups were defined if their hypoxia score was in the upper half of all hypoxia scores, and patients in low-score groups if their hypoxia score were in the lower half. GSEA was applied to detect the functional pathway of these differently expressed genes. CIBERSORT algorithm was utilized to evaluate the tumor-infiltrating immune cells of SCZ patients. In this study, we developed and validated a biomarker consisting of 12 hypoxia-related genes that could distinguish healthy controls and SCZ patients robustly. We found that the metabolism reprogramming might be activated in patient with high hypoxia score. Finally, CIBERSORT analysis illustrated that lower composition of naive B cells and higher composition of memory B cells might be observed in low-score groups of SCZ patients. These findings revealed that the hypoxia-related signature was acceptable as a detector for SCZ, providing further insight into effective diagnosis and treatment strategies for SCZ.