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Comprehensive analysis of differentially expressed miRNAs in aged mice presenting with postoperative cognitive dysfunction

ABSTRACT: Postoperative cognitive dysfunction (POCD) is a common postoperative complication observed in elderly patients. However, the underlying mechanisms of POCD remain unclear. MicroRNAs (miRNAs) which are involved in the pathogenesis of neurodegenerative diseases, may also affect POCD. To identify the relevant potential mechanisms, in this study, we comprehensively compared the expression profiles of miRNAs in 5 hippocampal tissues from POCD mice and 5 hippocampal tissues from control mice by microarray. A total of 128 miRNAs, whose expression changed significantly, were identified. Four miRNAs were confirmed by quantitative real-time polymerase chain reaction (PCR) in 10 paired samples. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed to explore the principal functions of the deregulated genes. We predicted the potential targets of miRNAs by using bioinformatics methods. In summary, novel miRNAs were identified as potential biomarkers and therapeutic targets for POCD treatment.

ORGANISM(S): Mus musculus synthetic construct

PROVIDER: GSE95070 | GEO | 2017/02/20

SECONDARY ACCESSION(S): PRJNA375930

REPOSITORIES: GEO

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Project description:Treatment options and reliable predictive marker to determine patients at risk to develop postoperative LD and to define the optimal time point of liver resection are limited. Accordingly, there is an urgent need for an easily assessable preoperative test to predict postoperative liver function recovery, specifically as current markers are often expensive, time consuming and sometimes invasive. Emerging evidence suggests that microRNA (miRNA) signatures represent potent diagnostic, prognostic and treatment response biomarkers for several diseases. Using next-generation sequencing as an unbiased systematic approach 554 miRNAs were detected in preoperative plasma of 21 patients suffering from postoperative LD after liver resection and 27 matched controls. Subsequently, we identified a miRNA signature - consisting of miRNAs 151a-5p, 192-5p and 122-5p - that highly correlated with patients developing postoperative LD after liver resection. The predictive potential for postoperative LD was subsequently confirmed using real-time PCR in an independent validation cohort of 98 patients. Ultimately, a regression model of the two miRNA ratios 151a-5p to 192-5p and 122-5p to 151a-5p was found to reliably predict postoperative LD, severe morbidity, prolonged intensive care unit and hospital stay and even mortality prior to surgery with a remarkable accuracy, thereby outperforming established markers of postoperative LD. Ultimately, we documented that miRNA ratios closely followed liver function recovery after partial hepatectomy. Conclusion: Given the clinical relevance of predicting potentially fatal postoperative clinical outcome after liver resection, our data demonstrate the clinical utility of a novel miRNA-based biomarker to support the selection of patients undergoing partial hepatectomy. The dynamical changes during liver function recovery indicate a possible role in tailoring the optimal time point of surgery to each individual patient. Thereby, our data might help to tailor surgical strategies to the specific risk profile of individual patients.

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Comprehensive analysis of differentially expressed miRNAs in aged mice presenting with postoperative cognitive dysfunction

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