Chen Li, Yu Lili, Zhang Rixin, Zhu Ling, Shen Wanqi
Clinical Laboratory, the Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University.
Department of Hepatobiliary & Pancreatic Surgery, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Medicine (Baltimore). 2020 May 29;99(22):e19754. doi: 10.1097/MD.0000000000019754.
Previous studies have indicated the association of microRNA-146a/b (miR-146a/miR-146b) with pro-inflammatory cytokines production, lipopolysaccharide-mediated injuries and organ dysfunction, however, the correlation of miR-146a/miR-146b with disease risk, disease severity, biochemical indices, inflammatory cytokines and mortality of sepsis has not been explored, which was investigated in the present study.
In total, 180 sepsis patients and 180 healthy controls were enrolled. The peripheral blood samples were collected from sepsis patients within 24 hour after admission and from healthy controls at enrolment. Furthermore, MiR-146a/miR-146b expressions in plasma were detected by reverse transcription quantitative polymerase chain reaction.
MiR-146a and miR-146b expressions were higher in sepsis patients compared to healthy controls. MiR-146a (AUC: 0.774, 95%CI: 0.727-0.820) and miR-146b (AUC: 0.897, 95%CI: 0.865-0.929) were both of good value in predicting increased sepsis risk, among which miR-146b presented a superior predictive value. In sepsis patients, MiR-146a expression was positively associated with miR-146b expression. Besides, MiR-146a and miR-146b expressions were positively correlated with acute pathologic and chronic health evaluation II score, sequential organ failure assessment score, serum creatinine, C-reactive protein, tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-17, while negatively correlated with albumin. Based on the survival status in 28-day follow-up, MiR-146a and miR-146b expression were both increased in survivors compared to deaths. miR-146b presented relatively good predictive for increased 28-day mortality risk (AUC: 0.703, 95%CI: 0.617-0.788), but MiR-146a was of poor value in predicting increased 28-day mortality risk (AUC: 0.599, 95%CI: 0.511-0.688).
MiR-146b presents superior potential as a prognostic biomarker in sepsis patients compared to MiR-146a, which implies the clinical application of miR-146b in disease management of sepsis.
既往研究表明微小RNA-146a/b（miR-146a/miR-146b）与促炎细胞因子产生、脂多糖介导的损伤及器官功能障碍有关，然而，miR-146a/miR-146b与脓毒症的疾病风险、疾病严重程度、生化指标、炎性细胞因子及死亡率之间的相关性尚未得到探究，本研究对此进行了调查。
共纳入180例脓毒症患者和180例健康对照。在脓毒症患者入院后24小时内及健康对照入组时采集外周血样本。此外，采用逆转录定量聚合酶链反应检测血浆中miR-146a/miR-146b的表达。
与健康对照相比，脓毒症患者中miR-146a和miR-146b的表达更高。miR-146a（曲线下面积：0.774，95%可信区间：0.727 - 0.820）和miR-146b（曲线下面积：0.897，95%可信区间：0.865 - 0.929）在预测脓毒症风险增加方面均具有良好价值，其中miR-146b具有更高的预测价值。在脓毒症患者中，miR-146a表达与miR-146b表达呈正相关。此外，miR-146a和miR-146b表达与急性病理和慢性健康评估II评分、序贯器官衰竭评估评分、血清肌酐、C反应蛋白、肿瘤坏死因子-α、白细胞介素（IL）-1β、IL-6、IL-17呈正相关，而与白蛋白呈负相关。根据28天随访的生存状态，与死亡患者相比，存活患者中miR-146a和miR-146b表达均升高。miR-146b在预测28天死亡风险增加方面具有相对较好的预测价值（曲线下面积：0.703，95%可信区间：0.617 - 0.788），但miR-146a在预测28天死亡风险增加方面价值较差（曲线下面积：0.599，95%可信区间：0.511 - 0.688）。
与miR-146a相比，miR-146b在脓毒症患者中作为预后生物标志物具有更高的潜力，这意味着miR-146b在脓毒症疾病管理中的临床应用价值。
