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The potential biomarkers for thromboembolism detected by SELDI-TOF-MS
Authors:Hong Mei  Zhang Xiaoping  Hu Yu  Wang Huafang  He Wenjuan  Mei Heng  Yu Jiekai  Guo Tao  Song Shanjun
Institution:a Institute of Hematology, Affiliated Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
b Key Laboratory of Biological Targeted Therapy of Hubei Province, Wuhan, China
c Cancer Institute, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
Abstract:

Introduction

Few studies were concerned about searching for specific biomarkers for thromboembolic (arterial and venous) diseases by the use of Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS).

Materials and Methods

We screened for potential biomarkers in 69 plasma samples, including samples from 20 patients with idiopathetic deep vein thrombosis (DVT), 20 patients with acute myocardial infarction (AMI), and 29 healthy controls without a history of thromboembolism. Pretreated plasma samples were analyzed on the Protein Biology System IIc plus SELDI-TOF-MS (Ciphergen Biosystems, Fremont, CA). Proteomic spectra of mass to charge ratio (m/z) were generated by the application of plasma to immobilized metal affinity capture (IMAC-3) ProteinChip arrays activated with copper.

Results

A pattern of three biomarkers (m/z: 2 667, 5 914, and 6 890 Da, respectively) with a total accuracy of 100% was selected based on their collective contribution to the optimal separation between patients with AMI and healthy controls. Another spattern consisting of only one biomarker (m/z: 5 914 Da) could totally discriminate patients with DVT and control subjects. For further analysis between patients with AMI and those with DVT, a pattern of four biomarkers (m/z: 3 418, 5 271, 33 378, and 68 125 Da, respectively) was selected with a total accuracy of 82.5%.

Conclusions

Plasma proteomic profiling with SELDI-TOF-MS and ProteinChip technologies provides high sensitivity and specificity in discriminating patients with thrombosis and healthy subjects. The discovered biomarkers might show great potential for early diagnosis of thromboembolic diseases.
Keywords:SELDI-TOF-MS  Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry  DVT  deep vein thrombosis  AMI  acute myocardial infarction  m/z  mass to charge ratio  IMAC-3  immobilized metal affinity capture  CUS  compression ultrasonography  PGV  platelet glycoprotein V  ECG  electrocardiogram  PE  pulmonary embolism  PBS  Protein Biology System  SPA  sinapinic acid  ZUCI-PDAS  Zhejiang University Cancer Institute-ProteinChip Data Analysis System  UDWT  undecimated discrete wavelet transform  S/N  signal-to-noise ratio  SVM  support vector machine  CV  coefficient of variation  ROC  receiver operator characteristic  CI  confidence interval  AUC  areas under the ROC curves  SVT  superficial venous thrombosis
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