Studies On Serum Proteomic Fingerprints Of Cardiac Dysfunction Caused By SELDI-TOF-MS

Objective To explore the serum proteomic fingerprints of cardiac dysfunction (CD) caused by coronary heart disease (CHD), in order to screen biomarkers of the differently expressed proteins of the different cardiac function grades, which would be sensitive indexes in discriminating cardiac function grades of CD and useful to monitor whether the patients were recurrent and precautioning in the early stage.Methods Sera were collected from 54 CHD patients with cardiac dysfunction and 18 CHD patients without cardiac dysfunction. We used SELDI-TOF mass spectrometry (manufactured by Cipergen Biosystems Inc, Fermont, CA, USA) and CM10 protein arrays to compare protein profiles from sera of 4 defined patient groups. Samples from patients with gradeâ…¡cardiac function (N=13), patients with gradeâ…¢cardiac function (N=13), patients with gradeâ…£cardiac function (N=14) and patients with gradeâ… cardiac function (N=18) as control were analyzed. The obtained spectra were subjected to bioinformatic analysis using BMW(Biomarker Wizard)and BPS 5.0 ( Biomarker patterns systems) .The classification decision tree (CDT) of cardiac dysfunction grading were established. At last we performed a blind trial by using this diagnostic cast.Results In the range of M/Z values 1000-100000 Da,68 protein peaks were dectected which had statistical difference between the CD group caused by coronary heart disease(CHD) and its control group(p<0.05) by the analysis of Biomarker Wizard Software, among which 9 peaks had statistical predominant difference (p<0.001). 3 biomarkers with M/Z of 2673,3151,15343Da were up-regulated while 6 biomarkers with M/Z 2733,2798,3932,4091,4298,5638Da were down-regulated in patients with CD.With the development of cardiac function grade, some discriminatory protein peaks such as the protein peak of 3279Da were down-regulated firstly and then up-regulated, while the protein peaks of 2733 Da and 4091Da were down-regulated gradually. We established the classification diagnostic tree of cardiac function grade by combined 2 protein peaks with M/Z 2733,3279 Da using BPS. Its sensitivity, specificity and positive predictive values were over 90%, and the CDT could distinguish cardiac function gradeâ… andâ…£with acuracy of 100%. Using this diagnostic cast, we performed a blind trial to another 27 serum samples from patients with the CD and 9 serum samples from control group and the values of sensitivity, specificity and positive predictive were over 80%.Conclusions SELDI-TOF-MS combined with protein chip technology could greatly facilitate discovery of biological markers of CD. The diagnostic pattern ,which established by distinguished protein with M/Z 2733,3279Da with high sensitivity, specificity and positive predictive value, could be useful to identify different cardiac function grade of CD from patient control, and had clinical significance for monitoring whether the patients were recurrent and for precautioning in the early stage.