Molecular RNA Correlates of the SOFA Score in Patients with Sepsis

Abstract

The most common scoring system for critically ill patients is the Sequential Organ Failure Assessment (SOFA) score. Little is known about specific molecular signaling networks underlying the SOFA criteria. We characterized these networks and identified specific key regulatory molecules. We prospectively studied seven patients with sepsis and six controls with high-throughput RNA sequencing (RNAseq). Quantitative reverse transcription PCR (RT-qPCR) confirmation was performed in a second independent cohort. Differentially and significantly expressed miRNAs and their target mRNA transcripts were filtered for admission SOFA criteria and marker RNAs for the respective criteria identified. We bioinformatically constructed molecular signaling networks specifically reflecting these criteria followed by RT-qPCR confirmation of RNAs with important regulatory functions in the networks in the second cohort. RNAseq identified 82 miRNAs (45% upregulated) and 3254 mRNAs (50% upregulated) differentially expressed between sepsis patients and controls. Bioinformatic analysis characterized 6 miRNAs and 76 mRNA target transcripts specific for the SOFA criteria. RT-qPCR validated miRNA and mRNAs included IGFBP2 (respiratory system); MMP9 and PDE4B (nervous system); PPARG (cardiovascular system); AKR1B1, ANXA1, and LNC2/NGAL (acute kidney injury); GFER/ALR (liver); and miR-30c-3p (coagulopathy). There are specific canonical networks underlying the SOFA score. Key regulatory miRNA and mRNA transcripts support its biologic validity.

Applying Transcriptomics for an Enhanced Clinical Research Framework, Implications for an Improved Research Strategy based on an Omics Approach: A Scoping Review

“…Using the Sequential Organ Failure Assessment (SOFA) score, Meidert et al compared septic patients with controls to describe molecular networks (58). Criteria included hypoxia, impaired Glasgow Coma Score, circulatory failure, a low platelet count, and increased serum creatinine and bilirubin.…”

“…Scoring systems such as the well-established SOFA score help predict the outcome. Meidert et al used a miRNA and mRNA gene expression to subgroup according to specific SOFA criteria(58). Other classifications include ARDS versus non-ARDS (57).…”

“…Also, functional enrichment analysis demonstrated an altered immune response in sepsis-induced ARDS. Further, using protein-protein interaction network analysis, the TOP2A gene was identified as a critical regulator in sepsis-induced ARDS.Using the Sequential Organ Failure Assessment (SOFA) score, Meidert et al compared septic patients with controls to describe molecular networks50 . Criteria included hypoxia, impaired Glasgow Coma Score, circulatory failure, a low platelet count, and increased serum creatinine and bilirubin.…”

Analysis of early risk factors for the lethal outcome of abdominal sepsis as indications for the start of invasive monitoring of central hemodynamics: a retrospective observational study

“…Оценка по SOFA, предложенная более 25 лет назад [21], сохраняет несо мненную актуальность при оценке риска летальности [22,23]. Более того, в настоящее время получены свидетельства связи компонентов этой шкалы с нарушениями при сепсисе внутриклеточных сигнальных пу тей, изменениями уровня матричной и митохондриальной РНК [24]. Указывают, что кардиальная подшкала SOFA в первые 24 ч нахождения в ОРИТ может стратифицировать риск летальности у больных с сепсисом и сопутствующими сердечно-сосудистыми заболеваниями, а также при сочетании септического и кардиогенного шока [25].…”

Prognostic value of von Willebrand factor and ADAMTS13 in patients with COVID-19: A systematic review and meta-analysis

“…We also found that hyperadhesive VWF released during acute traumatic brain injury mediated EVs to active ECs and platelets, thus responsible for consumptive coagulopathy and vascular leakage in the brain and the lung [31,32]. Increased circulating EVs, containing procoagulant, proinflammatory, and prothrombotic factors in their cargo, have been reported to be predictive biomarkers and likely to enhance immunothrombosis in patients with COVID-19 [130][131][132][133][134][135][136]. Hence, VWF tethered EVs (VWF + EVs) may also be involved in COVID-19-associated endotheliopathy and coagulopathy, and a promising diagnostic or prognostic marker.…”