Perioperative gene expression analysis for prediction of postoperative sepsis.
BACKGROUND
Postoperative sepsis is one of the main causes of death after major abdominal surgery; however, the immunologic factors contributing to the development of sepsis are not completely understood. In this study, we evaluated gene expression in patients who developed postoperative sepsis and in patients with an uncomplicated postoperative course.


METHODS
We enrolled 220 patients in a retrospective matched-pair, case-control pilot study to investigate the perioperative expression of 23 inflammation-related genes regarding their properties for predicting postoperative sepsis. Twenty patients exhibiting symptoms of sepsis in the first 14 days after surgery (case group) were matched with 20 control patients with an uncomplicated postoperative course. Matching criteria were sex, age, main diagnosis, type of surgery, and concomitant diseases. Blood samples were drawn before surgery and on the first and second postoperative days. Relative gene expression was analyzed with real-time reverse-transcription PCR.


RESULTS
Significant differences (P < 0.005) in gene expression between the 2 groups were observed for IL1B (interleukin 1, beta), TNF [tumor necrosis factor (TNF superfamily, member 2)], CD3D [CD3d molecule, delta (CD3-TCR complex)], and PRF1 [perforin 1 (pore forming protein)]. Logistic regression analysis and a subsequent ROC curve analysis revealed that the combination of TNF, IL1B, and CD3D expression had a specificity and specificity of 90% and 85%, respectively, and predicted exclusion of postoperative sepsis with an estimated negative predictive value of 98.1%.


CONCLUSIONS
These data suggest that gene expression analysis may be an effective tool for differentiating patients at high and low risk for sepsis after abdominal surgery.
Department of Medical Immunology, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
Carl
C
Hinrichs
Katja
K
Kotsch
Sandra
S
Buchwald
Marit
M
Habicher
Nicole
N
Saak
Herwig
H
Gerlach
Hans-Dieter
HD
Volk
Didier
D
Keh
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017252:CD3 Complex / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D054353:Perforin; D010865:Pilot Projects; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics*; D011183:Postoperative Complications; D011237:Predictive Value of Tests; D012372:ROC Curve; D012044:Regression Analysis; D015203:Reproducibility of Results; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D018805:Sepsis / Q000235:genetics* / Q000601:surgery; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D017252:CD3 Complex; C472562:CD3delta antigen; C508585:IL1B protein, human; D053583:Interleukin-1beta; C510468:PRF1 protein, human; D052899:Pore Forming Cytotoxic Proteins; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin