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.
BACKGROUND
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.


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-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.


CONCLUSIONS
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.
Division of Anesthesiology and Critical Care Medicine, Tottori University School of Medicine, Nishicho 36-1, Yonago, Tottori 683-8503, Japan.
Shunsaku
S
Takahashi
Norimasa
N
Miura
Tomomi
T
Harada
ZhongZhi
Z
Wang
Xinhui
X
Wang
Hideyuki
H
Tsubokura
Yoshiaki
Y
Oshima
Junichi
J
Hasegawa
Yoshimi
Y
Inagaki
Goshi
G
Shiota
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics; D004938:Esophageal Neoplasms / Q000097:blood / Q000235:genetics* / Q000601:surgery; D016629:Esophagectomy; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007362:Intensive Care Units; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000235:genetics; D054409:Nicotinamide Phosphoribosyltransferase / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics; D014841:von Willebrand Factor / Q000235:genetics
D016207:Cytokines; D015850:Interleukin-6; D018396:Mucin-1; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014841:von Willebrand Factor; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human