Genome-wide blood transcriptional profiling in critically ill patients - MARS consortium

The host response in critically ill patients with sepsis, septic shock remains poorly defined. Considerable research has been conducted to accurately distinguish patients with sepsis from those with non-infectious causes of disease. Technological innovations have positioned systems biology at the forefront of biomarker discovery. Analysis of the whole-blood leukocyte transcriptome enables the assessment of thousands of molecular signals beyond simply measuring several proteins in plasma, which for use as biomarkers is important since combinations of biomarkers likely provide more diagnostic accuracy than the measurement of single ones or a few. Evidence suggests that genome-wide transcriptional profiling of blood leukocytes can assist in differentiating between infection and non-infectious causes of severe disease. Of importance, RNA biomarkers have the potential advantage that they can be measured reliably in rapid quantitative reverse transcriptase polymerase chain reaction (qRT-PCR)-based point of care tests. PAXgene blood RNA was isolated at intensive-care unit (ICU) admission and throughout ICU length-of-stay. Through the use of genome-wide microarrays we aimed to identify molecular features that enbale the adequate discrimination of infectious and non-infectious sources of critical illness. Patient diagnoses include community-acquired pneumonia (cap), hospital-acquired pneumonia (hap) and non-infectious cap control patients (no-cap) (characteristics: pneumonia diagnoses). The influence of variable degrees of thrombocytopenia were also assessed (characteristics: thrombocytopenia).

脓毒症、感染性休克重症患者的宿主应答机制迄今仍未被充分阐明。目前已有大量研究致力于精准区分脓毒症患者与非感染性疾病患者。技术革新使得系统生物学（systems biology）成为生物标志物发现领域的前沿方向。全血白细胞转录组分析能够同时检测数千种分子信号，而非仅检测血浆中的数种蛋白质；相较于单一或少量生物标志物检测，多生物标志物联合检测可提供更高的诊断准确性，因此该分析方法在生物标志物应用中具有重要价值。已有研究表明，血液白细胞的全基因组转录谱分析有助于区分重症疾病的感染性与非感染性病因。值得注意的是，RNA生物标志物具备一项潜在优势：可通过基于快速定量反转录聚合酶链反应（qRT-PCR）的床旁检测实现可靠定量。本研究在重症监护病房（intensive-care unit, ICU）收治时及患者整个ICU住院期间，采集并分离PAXgene管全血RNA。本研究通过全基因组微阵列技术，旨在筛选可精准区分重症疾病感染性与非感染性病因的分子特征。研究纳入的患者诊断包括社区获得性肺炎（community-acquired pneumonia, CAP）、医院获得性肺炎（hospital-acquired pneumonia, HAP）以及非感染性CAP对照患者（non-infectious CAP control patients, NO-CAP），相关特征标注为「肺炎诊断」。本研究同时评估了不同程度血小板减少症对研究结果的影响，相关特征标注为「血小板减少症」。