Serum Messenger RNA as a Biomarker and its Clinical Usefulness in Malignancies

A number of biomarkers are used clinically and many protein-based assay methods are available. Improvements in the method to utilize specific antibodies have led to remarkable progress in clinical diagnosis using biomarkers. Proteomics studies to identify better biomarkers have been performed worldwide by using a protein-based comprehensive method. The detection rate of conventional biomarkers can not improve further. Now is a time that a breakthrough is needed. We previously proposed mRNA, which is circulating in the body, as a novel material for biomarkers. mRNA is an unexpectedly useful molecule, not only because it can detect genes with a low expression level in protein, but also because it can detect the expression from non-coding RNA precursor genes or gene products with limited secretion from the cells. Circulating mRNA has been thought to be unstable in blood containing RNase. We confirm that mRNA remains at the same level for 24 hours after blood sampling. Unlike DNA, the RNA molecule can reflect events in the human body which occurred within a day, resulting in an early diagnosis of diseases. We report the possibility to detect and quantify cancer-derived mRNAs circulating in human vessels. We introduce the detection of serum mRNA as a useful biomarker of human malignancies

Analysis of Heart Rate Variability before and after Catheter Ablation for Atrial Flutter with Complicating Atrial Fibrillation

Efficacy of radiofrequency (RF) catheter ablation in suppressing atrial fibrillation (AF) was studied by analysis of heart rate variability (HRV) in 13 patients with atrial flutter complicated with AF. We treated these patients by RF ablation of the isthmus between the tricuspid valve annulus and the inferior vena cava to create a bidirectional conduction block. To analyze the HRV, 24-h ambulatory electrocardiographic monitoring was performed 1 day before, 1 day after and 1 month after the ablation. After the RF ablation of the isthmus, 7 patients continued to experience AF attacks, while the remaining 6 patients did not. We divided them into 2 groups, attacked by AF (AF group) and not attacked by AF (non-AF group), and analyzed HRV parameters. The results obtained were compared between the groups. One month after the ablation, the non-AF group showed a significantly higher average heart rate than the AF group. The HRV parameters indicating cardiac vagal nervous activities, such as the root-mean-square of differences, percentage of adjacent normal RR intervals and high frequency power, were significantly lower in the non-AF group 1 month after. Furthermore, the ratio of low frequency power to high frequency power, which is a measure for cardiac sympathetic nervous activity, was significantly higher in the non-AF group 1 month after. From these results, we postulate that the suppression of postoperative AF may involve vagal nerve suppression and sympathetic nerve activation

Prognostic impact of clinical course-specific mRNA expression profiles in the serum of perioperative patients with esophageal cancer in the ICU: a case control study

<p>Abstract</p> <p>Background</p> <p>We 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.</p> <p>Methods</p> <p>We 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.</p> <p>Results</p> <p>Circulating 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.</p> <p>Conclusion</p> <p>Chronological 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.</p