Abstract
There is an increasing interest in searching biomarkers for schizophrenia (SZ) diagnosis, which overcomes the drawbacks inherent with the subjective diagnostic methods. MicroRNA (miRNA) fingerprints have been explored for disease diagnosis. We performed a meta-analysis to examine miRNA diagnostic value for SZ and further validated the meta-analysis results. Using following terms: schizophrenia/SZ, microRNA/miRNA, diagnosis, sensitivity and specificity, we searched databases restricted to English language and reviewed all articles published from January 1990 to October 2016. All extracted data were statistically analyzed and the results were further validated with peripheral blood mononuclear cells (PBMNCs) isolated from patients and healthy controls using RT-qPCR and receiver operating characteristic (ROC) analysis. A total of 6 studies involving 330 patients and 202 healthy controls were included for meta-analysis. The pooled sensitivity, specificity and diagnostic odds ratio were 0.81 (95% CI: 0.75-0.86), 0.81 (95% CI: 0.72-0.88) and 18 (95% CI: 9-34), respectively; the positive and negative likelihood ratio was 4.3 and 0.24 respectively; the area under the curve in summary ROC was 0.87 (95% CI: 0.84-0.90). Validation revealed that miR-181b-5p, miR-21-5p, miR-195-5p, miR-137, miR-346 and miR-34a-5p in PBMNCs had high diagnostic sensitivity and specificity in the context of schizophrenia. In conclusion, blood-derived miRNAs might be promising biomarkers for SZ diagnosis.
Highlights
There is an increasing interest in searching biomarkers for schizophrenia (SZ) diagnosis, which overcomes the drawbacks inherent with the subjective diagnostic methods
Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and receiver operating characteristic (ROC) analysis, we validated 6 miRNAs identified in the meta-analysis with peripheral blood mononuclear cells (PBMNCs) isolated from 39 patients and 50 healthy controls
Molecular examinations have discovered aberrant gene expression including miRNAs in different sources of samples, e.g., the brain tissue, plasma, serum and PBMNCs, derived from patients with SZ24–40, raising the possibility that certain gene expression patterns distinctively present in patients might be useful for SZ diagnosis and/or treatment monitoring[33,37,39,40,42–49]
Summary
There is an increasing interest in searching biomarkers for schizophrenia (SZ) diagnosis, which overcomes the drawbacks inherent with the subjective diagnostic methods. MicroRNAs (miRNAs) are a class of small non-coding RNAs (approximately 19–22 nucleotides in length) that are generally believed to negatively regulate gene expression, thereby controlling a wide range of biological processes and functions[1,2] They bind sequences in the target messenger RNA 3′-untranslated regions through complementarity and form RNA-RNA complex, leading eventually to mRNA degradation or translational inhibition[3,4]. We conducted a systematic review on findings in blood-derived miRNA expression in patients with SZ, and performed a meta-analysis to evaluate the diagnostic value of blood-derived miRNAs. using RT-qPCR and receiver operating characteristic (ROC) analysis, we validated 6 miRNAs identified in the meta-analysis with peripheral blood mononuclear cells (PBMNCs) isolated from 39 patients and 50 healthy controls
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