基于 Solexa 测序的血清 microRNA 特征可预测脓毒症患者的死亡率：一项前瞻性观察研究。
Serum microRNA signatures identified by Solexa sequencing predict sepsis patients' mortality: a prospective observational study.
机构信息
Department of Respiratory Medicine, Hainan Branch of Chinese PLA General Hospital, Sanya, Hainan Province, China.
出版信息
PLoS One. 2012;7(6):e38885. doi: 10.1371/journal.pone.0038885. Epub 2012 Jun 15.
BACKGROUND
Sepsis is the leading cause of death in Intensive Care Units. Novel sepsis biomarkers and targets for treatment are needed to improve mortality from sepsis. MicroRNAs (miRNAs) have recently been used as finger prints for sepsis, and our goal in this prospective study was to investigate if serum miRNAs identified in genome-wide scans could predict sepsis mortality.
METHODOLOGY/PRINCIPAL FINDINGS: We enrolled 214 sepsis patients (117 survivors and 97 non-survivors based on 28-day mortality). Solexa sequencing followed by quantitative reverse transcriptase polymerase chain reaction assays was used to test for differences in the levels of miRNAs between survivors and non-survivors. miR-223, miR-15a, miR-16, miR-122, miR-193*, and miR-483-5p were significantly differentially expressed. Receiver operating characteristic curves were generated and the areas under the curve (AUC) for these six miRNAs for predicting sepsis mortality ranged from 0.610 (95%CI: 0.523-0.697) to 0.790 (95%CI: 0.719-0.861). Logistic regression analysis showed that sepsis stage, Sequential Organ Failure Assessment scores, Acute Physiology and Chronic Health Evaluation II scores, miR-15a, miR-16, miR-193b*, and miR-483-5p were associated with death from sepsis. An analysis was done using these seven variables combined. The AUC for these combined variables' predictive probability was 0.953 (95% CI: 0.923-0.983), which was much higher than the AUCs for Acute Physiology and Chronic Health Evaluation II scores (0.782; 95% CI: 0.712-0.851), Sequential Organ Failure Assessment scores (0.752; 95% CI: 0.672-0.832), and procalcitonin levels (0.689; 95% CI: 0.611-0.784). With a cut-off point of 0.550, the predictive value of the seven variables had a sensitivity of 88.5% and a specificity of 90.4%. Additionally, miR-193b* had the highest odds ratio for sepsis mortality of 9.23 (95% CI: 1.20-71.16).
CONCLUSION/SIGNIFICANCE: Six serum miRNA's were identified as prognostic predictors for sepsis patients.
TRIAL REGISTRATION
ClinicalTrials.gov NCT01207531.
背景
败血症是重症监护病房死亡的主要原因。需要新的败血症生物标志物和治疗靶点来提高败血症的死亡率。微小 RNA（miRNA）最近被用作败血症的指纹，我们在这项前瞻性研究中的目标是研究全基因组扫描中鉴定的血清 miRNA 是否可以预测败血症的死亡率。
方法/主要发现：我们招募了 214 例败血症患者（根据 28 天死亡率，117 例存活者和 97 例非存活者）。采用 Solexa 测序和定量逆转录聚合酶链反应检测存活者和非存活者之间 miRNA 水平的差异。miR-223、miR-15a、miR-16、miR-122、miR-193和 miR-483-5p 的表达水平差异显著。生成了受试者工作特征曲线，这 6 种 miRNA 预测败血症死亡率的曲线下面积（AUC）范围为 0.610（95%CI：0.523-0.697）至 0.790（95%CI：0.719-0.861）。Logistic 回归分析显示，败血症分期、序贯器官衰竭评估评分、急性生理学和慢性健康评估 II 评分、miR-15a、miR-16、miR-193b和 miR-483-5p 与败血症死亡相关。对这 7 个变量进行了综合分析。这些综合变量预测概率的 AUC 为 0.953（95%CI：0.923-0.983），明显高于急性生理学和慢性健康评估 II 评分（0.782；95%CI：0.712-0.851）、序贯器官衰竭评估评分（0.752；95%CI：0.672-0.832）和降钙素水平（0.689；95%CI：0.611-0.784）。当截断值为 0.550 时，7 个变量的预测值具有 88.5%的灵敏度和 90.4%的特异性。此外，miR-193b*的败血症死亡率的比值比最高，为 9.23（95%CI：1.20-71.16）。
结论/意义：发现 6 种血清 miRNA 可作为败血症患者的预后预测因子。
试验注册
ClinicalTrials.gov NCT01207531。
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