YKL-40 IDENTIFIED BY PROTEOMIC ANALYSIS AS A BIOMARKER OF SEPSIS
YKL-40 IDENTIFIED BY PROTEOMIC ANALYSIS AS A BIOMARKER OF SEPSIS
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DOI：
10.1097/shk.0b013e31819e2c0c
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发表时间：
2009-10-01
期刊：
影响因子：
3.1
通讯作者：
Hirasawa, Hiroyuki
中科院分区：
文献类型：
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作者：
Hattori, Noriyuki;Oda, Shigeto;Hirasawa, Hiroyuki
通过蛋白质组学分析研究脓毒症患者血清中蛋白质表达的变化，并鉴定脓毒症的新生物标志物。共有45例连续严重脓毒症或脓毒性休克患者（脓毒症组），22例健康志愿者和23例接受非体外循环冠状动脉旁路移植术的患者（对照组）。每组8例患者的血清样本进行蛋白质组学分析，包括去除12种主要蛋白质，随后进行反相高效液相色谱分离和一维电泳。脓毒症组41条谱带（鉴定出12种蛋白）强度增加，42条谱带（鉴定出22种蛋白）强度降低。蛋白质组学分析结果通过Western印迹和/或酶联免疫吸附测定法成功验证了脓毒症组中三种蛋白质（YKL-40，脂质运载蛋白2和S100 A9）增加以及两种蛋白质（视黄醇结合蛋白，维生素D结合蛋白）减少。采用酶联免疫吸附法检测两组患者入院时血清YKL-40水平，结果脓毒症组血清YKL-40水平明显高于对照组（P < 0.001）。血培养阳性患者（P < 0.005）、感染性休克患者（P <0.05）、后续治疗中需要连续性血液透析滤过（P <0.05）或氢化可的松替代治疗（P <0.005）的患者入院时sYKL-40显著升高。脓毒症组入院时sYKL-40与IL-6水平呈正相关（r = 0.465，P < 0.01）。通过蛋白质组学分析鉴定的YKL-40被认为是脓毒症的生物标志物。然而，需要进一步的研究来阐明其作为生物标志物的作用和临床实用性。
To investigate changes in protein expression by proteomic analysis in the sera of patients with sepsis and to identify new biomarkers of sepsis. A total of 45 consecutive patients with severe sepsis or septic shock (sepsis group), 22 healthy volunteers, and 23 patients undergoing off-pump coronary artery bypass grafting (control group). Serum samples from eight patients of each group underwent proteomic analysis involving removal of 12 major proteins and subsequent reversed-phase high-performance liquid chromatography fractionation and one-dimensional electrophoresis. The intensity of 41 bands (with 12 proteins identified) increased and that of 42 bands (with 22 proteins identified) decreased in the sepsis group. Results of proteomic analysis successfully validated by Western blotting and/or enzyme-linked immunosorbent assay for three proteins (YKL-40, lipocalin 2, and S100A9) increased in the sepsis group as well as two proteins (retinol-binding protein, vitamin D-binding protein) decreased. Serum YKL-40 levels (sYKL-40) on intensive care unit (ICU) admission were assessed by enzyme-linked immunosorbent assay between the two groups; resulting YKL-40 was significantly higher in the sepsis group (P < 0.001). Furthermore, sYKL-40 on ICU admission was significantly higher in patients with positive blood culture (P < 0.005), patients with septic shock (P < 0.05), and patients requiring continuous hemodiafiltration (P < 0.05) or hydrocortisone replacement therapy (P < 0.005) during subsequent treatment. A positive correlation between sYKL-40 and blood IL-6 level on ICU admission was noted in the sepsis group (r = 0.465, P < 0.01). YKL-40 identified by proteomic analysis is considered as a biomarker of sepsis. However, further investigation is needed to clarify its roles and clinical usefulness as a biomarker.