Prognostic impact of clinical course-specific mRNA expression profiles in the serum of perioperative patients with esoph
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RESEARCH
Open Access
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 Shunsaku Takahashi1,2, Norimasa Miura2*, Tomomi Harada1,2, ZhongZhi Wang2, Xinhui Wang2, Hideyuki Tsubokura3, Yoshiaki Oshima1,4, Junichi Hasegawa2, Yoshimi Inagaki1, Goshi Shiota5
Abstract Background: 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. Methods: 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. Results: 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-b1 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. Conclusion: 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.
Background Esophageal cancer is one of the most aggressive malignant tumors of the digestive tract. 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 * Correspondence: [email protected] 2 Division of Pharmacotherapeutics, Department of Pathophysiological and Therapeutic Science, Faculty of Medicine, Tottori University, Nishicho 86, Yonago, Tottori 683-8503, Japan Full list of author information is available at the end of the article
heterogeneous lung disease resulting in progressive hypoxemia due to ventilation/perfusion mismatching an
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