Identification of a high molecular weight kininogen fragment as a marker for early gastric cancer by serum proteome analysis
Identification of a high molecular weight kininogen fragment as a marker for early gastric cancer by serum proteome analysis
复制标题
DOI：
10.1007/s00535-010-0369-3
复制
发表时间：
2011-05-01
影响因子：
6.3
通讯作者：
Nomura, Fumio
中科院分区：
文献类型：
--
作者：
Umemura, Hiroshi;Togawa, Akira;Nomura, Fumio
利用基质辅助激光解吸/电离飞行时间质谱仪(MS)对81例胃癌患者和66例年龄、性别匹配的健康人血清样品进行了多肽图谱的比较分析。由于初步筛选和进一步验证，我们发现胃癌患者术前血清中一个2209 m/z的MS峰的强度增加，我们鉴定该峰是一个高相对分子质量(HMW)的激肽原片段。受试者工作特性分析显示，2209Da多肽的曲线下面积(AUC)(AUC=0.715)大于用于检测I期胃癌的常规肿瘤标志物(癌胚抗原AUC=0.593，糖类抗原19-9AUC=0.527)的曲线下面积。血清中完整的HMW激肽原水平与2209 Da肽水平呈负相关，提示某些蛋白酶活性上调是导致胃癌患者激肽原片段过度产生的原因。本研究中鉴定的2209 Da肽的血清水平比用于胃癌早期检测的传统肿瘤标志物具有更强的诊断能力。
Serum biomarkers currently available for gastric cancers are not sufficiently sensitive and specific.We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) to generate comparative peptide profiles of serum samples obtained from gastric cancer patients (n = 81) and age- and sex-matched healthy controls (n = 66).Because of initial screening and further validation, we found that the intensities of a 2209 m/z MS peak were increased in the preoperative sera obtained from gastric cancer patients, and we identified this peak, a 2209 Da peptide, as a high molecular weight (HMW) kininogen fragment. Receiver operating characteristic analyses showed that the area under the curve (AUC) for the 2209 Da peptide (AUC = 0.715) was greater than those for conventional tumor markers (carcinoembryonic antigen AUC = 0.593, carbohydrate antigen 19-9 AUC = 0.527) used for the detection of stage I gastric cancers. Inverse correlations were observed between the levels of intact HMW kininogen and the 2209 Da peptide, suggesting that the upregulation of some protease activities is responsible for the overproduction of a kininogen fragment in gastric cancer patients.Serum levels of the 2209 Da peptide identified in this study have a greater diagnostic ability than those of conventional tumor markers used for the early detection of gastric cancer.