Huang Jie, Sun Zhandong, Yan Wenying, Zhu Yujie, Lin Yuxin, Chen Jiajai, Shen Bairong, Wang Jian
Systems Sepsis Biology Team, Soochow University Affiliated Children's Hospital, Suzhou 215003, China.
Systems Sepsis Biology Team, Soochow University Affiliated Children's Hospital, Suzhou 215003, China ; Center for Systems Biology, Soochow University, Suzhou 215006, China.
Biomed Res Int. 2014;2014:594350. doi: 10.1155/2014/594350. Epub 2014 Apr 6.
Sepsis is regarded as arising from an unusual systemic response to infection but the physiopathology of sepsis remains elusive. At present, sepsis is still a fatal condition with delayed diagnosis and a poor outcome. Many biomarkers have been reported in clinical application for patients with sepsis, and claimed to improve the diagnosis and treatment. Because of the difficulty in the interpreting of clinical features of sepsis, some biomarkers do not show high sensitivity and specificity. MicroRNAs (miRNAs) are small noncoding RNAs which pair the sites in mRNAs to regulate gene expression in eukaryotes. They play a key role in inflammatory response, and have been validated to be potential sepsis biomarker recently. In the present work, we apply a miRNA regulatory network based method to identify novel microRNA biomarkers associated with the early diagnosis of sepsis. By analyzing the miRNA expression profiles and the miRNA regulatory network, we obtained novel miRNAs associated with sepsis. Pathways analysis, disease ontology analysis, and protein-protein interaction network (PIN) analysis, as well as ROC curve, were exploited to testify the reliability of the predicted miRNAs. We finally identified 8 novel miRNAs which have the potential to be sepsis biomarkers.
脓毒症被认为是由对感染的异常全身反应引起的,但脓毒症的生理病理学仍不清楚。目前,脓毒症仍然是一种致命疾病,诊断延迟且预后不良。许多生物标志物已在脓毒症患者的临床应用中被报道,并声称可改善诊断和治疗。由于难以解释脓毒症的临床特征,一些生物标志物并未显示出高敏感性和特异性。微小RNA(miRNA)是小的非编码RNA,可与mRNA中的位点配对以调节真核生物中的基因表达。它们在炎症反应中起关键作用,最近已被证实是潜在的脓毒症生物标志物。在本研究中,我们应用基于miRNA调控网络的方法来鉴定与脓毒症早期诊断相关的新型微小RNA生物标志物。通过分析miRNA表达谱和miRNA调控网络,我们获得了与脓毒症相关的新型miRNA。利用通路分析、疾病本体分析和蛋白质-蛋白质相互作用网络(PIN)分析以及ROC曲线来验证预测的miRNA的可靠性。我们最终鉴定出8种具有成为脓毒症生物标志物潜力的新型miRNA。