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

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.

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“…In contrast, Takahashi et al demonstrated that circulating eNAMPT levels are elevated in plasma of 27 pre‐oesophagectomy and post‐oesophagectomy patients. Despite having a small cohort, this study did also demonstrate that therapeutic treatment with sivelestat, a neutrophil elastase inhibitor, resulted in decreased eNAMPT levels (Takahashi et al , ). The disparate findings of these two independent studies may be explained in part by the methodology used to detect plasma eNAMPT.…”

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“…Moreover, the elevated concentration of circulating RNA has been shown to be closely associated with poor prognosis in esophageal cancer, breast cancer or lymphoma 17-19. The increase of circulating cell-free hTERT mRNA was demonstrated to be correlated with reduced disease-free survival and overall survival in gastric cancer patients by Kang et al 20.…”

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“…Takahashi et al [46] reported that TGF-β was upregulated in esophageal cancer patients. Others [40] have reported increased proliferation in esophageal cancer through P-38 and ERK-MAPK pathways.…”