利用 SELDI-TOF-MS 鉴定出五种血清蛋白作为胃癌的潜在生物标志物。

Five serum proteins identified using SELDI-TOF-MS as potential biomarkers of gastric cancer.

机构信息

Department of Oncology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.

出版信息

Jpn J Clin Oncol. 2010 Apr;40(4):336-42. doi: 10.1093/jjco/hyp175. Epub 2010 Jan 20.

DOI:10.1093/jjco/hyp175

PMID:20089528

Abstract

OBJECTIVE

The aims of this study were to detect serum proteomic patterns in gastric cancer serum samples using Surface-enhanced Laser Desorption/ionization-Time-of-flight-Mass Spectrometry ProteinChip array technology, to screen biomarker candidates, to build diagnostic models and to evaluate their clinical significance.

METHODS

Serum samples from patients with gastric cancer and normal healthy control subjects (n = 125) were analysed using surface-enhanced laser desorption/ionization technology. The spectra were generated on weak cation exchange (WCX2) chips, and protein peak clustering and classification analyses were established using Ciphergen Biomarker Wizard and Biomarker Pattern software, respectively. The diagnostic models were developed and validated by discriminant analysis. In addition, the results of the surface-enhanced laser desorption/ionization model were compared with the biomarkers carcinoembryonic antigen and carbohydrate antigen 199 in a subset of samples using a microparticle enzyme immunoassay.

RESULTS

Five protein peaks at 2046, 3179, 1817, 1725 and 1929 m/z were automatically chosen as components of the best biomarker pattern for diagnosis of gastric cancer. In addition, we identified a single protein peak at 4665 m/z, which could distinguish between stage I/II and stage III/IV gastric cancer with a specificity and sensitivity of 91.6% (11/12) and 95.4% (21/22), respectively. When this biomarker was validated in the second set of samples, the specificity and sensitivity were 91.7% (11/12) and 86.3% (19/22), respectively.

CONCLUSIONS

The present results suggest that serum surface-enhanced laser desorption/ionization protein profiling can distinguish patients with gastric cancer, and in particular stage I/II patients, from normal subjects with a relatively high sensitivity and specificity. Surface-enhanced Laser Desorption/ionization-Time-of-flight-Mass Spectrometry is a potential new diagnostic tool for the screening of gastric cancer.

摘要

目的

本研究旨在应用表面增强激光解吸/电离-飞行时间质谱蛋白质芯片技术检测胃癌血清样本中的血清蛋白质组图谱，筛选生物标志物候选物，建立诊断模型并评估其临床意义。

方法

采用表面增强激光解吸/电离技术分析 125 例胃癌患者和正常健康对照者的血清样本。将光谱生成于弱阳离子交换（WCX2）芯片上，使用Ciphergen Biomarker Wizard 和 Biomarker Pattern 软件分别进行蛋白峰聚类和分类分析。通过判别分析建立和验证诊断模型。此外，通过微粒子酶免疫测定法，在部分样本中比较表面增强激光解吸/电离模型的结果与癌胚抗原和糖类抗原 199 标志物。

结果

自动选择 2046、3179、1817、1725 和 1929 m/z 处的 5 个蛋白峰作为诊断胃癌的最佳生物标志物模式的组成部分。此外，我们还鉴定出一个位于 4665 m/z 处的单一蛋白峰，可将 I/II 期和 III/IV 期胃癌区分开来，其特异性和灵敏度分别为 91.6%（11/12）和 95.4%（21/22）。在第二组样本中验证该生物标志物时，特异性和灵敏度分别为 91.7%（11/12）和 86.3%（19/22）。