Department of Medical Immunology, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
Clin Chem. 2010 Apr;56(4):613-22. doi: 10.1373/clinchem.2009.133876. Epub 2010 Feb 4.
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.
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.
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%.
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.
术后脓毒症是腹部大手术后死亡的主要原因之一,但导致脓毒症发生的免疫因素尚不完全清楚。本研究评估了发生术后脓毒症和术后无并发症患者的基因表达。
我们对 220 例患者进行了回顾性配对病例对照试验研究,以研究与术后脓毒症相关的 23 种炎症相关基因的围手术期表达情况,及其对预测术后脓毒症的作用。术后 14 天内出现脓毒症症状的 20 例患者(病例组)与 20 例术后无并发症的患者(对照组)相匹配。匹配标准为性别、年龄、主要诊断、手术类型和并存疾病。分别于术前、术后第 1 天及第 2 天采集血样,采用实时逆转录聚合酶链反应分析相对基因表达。
病例组与对照组之间观察到 IL1B(白细胞介素 1,β)、TNF(肿瘤坏死因子[TNF 超家族,成员 2])、CD3D(CD3d 分子,δ(CD3-TCR 复合物))和 PRF1(穿孔素 1(形成孔的蛋白))的基因表达存在显著差异(P<0.005)。逻辑回归分析和随后的 ROC 曲线分析显示,TNF、IL1B 和 CD3D 表达的组合具有 90%和 85%的特异性和敏感性,分别预测术后脓毒症的阴性预测值为 98.1%。
这些数据表明,基因表达分析可能是一种有效的工具,可区分腹部手术后发生脓毒症和无脓毒症风险高的患者。