Abstract
BackgroundWe previously reported that measuring circulating serum mRNAs using quantitative one-step real-time RT-PCR was clinically useful for detecting malignancies and determining prognosis. The aim of our study was to find crucial serum mRNA biomarkers in esophageal cancer that would provide prognostic information for post-esophagectomy patients in the critical care setting.MethodsWe measured serum mRNA levels of 11 inflammatory-related genes in 27 post-esophagectomy patients admitted to the intensive care unit (ICU). We tracked these levels chronologically, perioperatively and postoperatively, until the two-week mark, investigating their clinical and prognostic significance as compared with clinical parameters. Furthermore, we investigated whether gene expression can accurately predict clinical outcome and prognosis.ResultsCirculating mRNAs in postoperative esophagectomy patients had gene-specific expression profiles that varied with the clinical phase of their treatment. Multivariate regression analysis showed that upregulation of IL-6, VWF and TGF-β1 mRNA in the intraoperative phase (p = 0.016, 0.0021 and 0.009) and NAMPT and MUC1 mRNA on postoperative day 3 (p < 0.01) were independent factors of mortality in the first year of follow-up. Duration of ventilator dependence (DVD) and ICU stay were independent factors of poor prognosis (p < 0.05). Therapeutic use of Sivelestat (Elaspol®, Ono Pharmaceutical Co., Ltd.) significantly correlated with MUC1 and NAMPT mRNA expression (p = 0.048 and 0.045). IL-6 mRNA correlated with hypercytokinemia and recovery from hypercytokinemia (sensitivity 80.9%) and was a significant biomarker in predicting the onset of severe inflammatory diseases.ConclusionChronological tracking of postoperative mRNA levels of inflammatory-related genes in esophageal cancer patients may facilitate early institution of pharamacologic therapy, prediction of treatment response, and prognostication during ICU management in the perioperative period.
Highlights
We previously reported that measuring circulating serum mRNAs using quantitative one-step realtime RT-PCR was clinically useful for detecting malignancies and determining prognosis
We previously reported that the measurement of human telomerase reverse transcriptase gene mRNA in serum is useful for the diagnosis of some malignancies
matrix metallopeptidase 9 (MMP9) and NAMPT (PBEF1) were similar in that both were upregulated from postoperative day (POD) 5 onwards
Summary
We previously reported that measuring circulating serum mRNAs using quantitative one-step realtime RT-PCR was clinically useful for detecting malignancies and determining prognosis. The aim of our study was to find crucial serum mRNA biomarkers in esophageal cancer that would provide prognostic information for postesophagectomy patients in the critical care setting. Post-esophagectomy anastomotic leak and pneumonia are common and can lead to acute respiratory distress syndrome (ARDS). Acute respiratory distress syndrome (ARDS) is a diffuse. The use of gene-expression profiling on a transcriptome level of peripheral blood mononuclear cells (PBMC) identifies signature genes that distinguish severe sepsis (SS) from noninfectious causes of systemic inflammatory response syndrome (SIRS), sepsis-related immunosuppression and reduced inflammatory response [6]. As there are currently no reliable genetic markers for use in ICU care and prognostication, we aimed to determine the clinical value of measuring circulating RNA in the serum of ICU patients [8]. Since circulating RNA remains stable for approximately 24 hours, its detection may reflect early changes in clinical status and may make it possible to predict morbidity and survival [9]
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