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SELDI-TOF Analysis Of Serum Protein Profiling To Build The Peptide Patterns Of The Intracranial Aneurysms

Posted on:2010-12-11Degree:MasterType:Thesis
Country:ChinaCandidate:J ZhouFull Text:PDF
GTID:2144360278977846Subject:Neurosurgery
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Objective: Intracranial aneurysm is a permanent expansion of the the intracranial artery, mainly due to the wall of congenital defects, atherosclerosis, high blood pressure and so on. The incidence rate in cerebrovascular accident is No.3, second only to cerebral thrombosis and hypertensive cerebral hemorrhage, the morbidity and mortality rate is very high. About 8 ~ 32% of the patients died after the first bleeding, the mortality of 1 year later is 60% and that of 2 years later is 85%. It's important to find a solution to make a correct diagnosis earlily and provide treatment timely to reduce mortality and improve the prognosis of the disease, because of the high risk of bleeding, but the etiology and pathology of the intracranial aneurysm is still not very clear nowadays. According to the differences in protein expression in the intracranial aneurysm (IA) patients, you can better understand the pathological changes to pave the way for find out the molecular markers in future. We analysised in the protein abundance and the m/s in the serum proteins of the IA and tSAH by seldi-tof-ms,then expected that it can be used to find out the serum biomakers of the IA. According to the different protein peaks,we build up a database ,then establised the diagnostic model combinded with the ANN to get a non-invasive diagnostic solution . Methods: 40 cases of intracranial aneurysms patients, male 35 cases, female 25 cases aged 29 ~ 61 year old , cerebral angiography and CTA confirmed the intracranial cystic aneurysm (or spindle) and then surgical treatmented; tSAH patients with 55 cases , who were all the traumatic cerebral concusion and laceration patients (GCS =9~15). No other congenital diseases or serious medical illness in patients and they hospitalized for the first time. Location: the anterior communicating artery in 21 cases,the posterior communicating artery in 18 cases, internal carotid artery bifurcation in 8 cases, the anterior cerebral artery in 6 cases, the middle cerebral artery in 3 cases, the top of basilar artery in 2 cases, the posterior cerebral artery in 2 cases. We used SELDI-TOF-MS to detect 40 cases of IAs'serum samples and 40 cases of tSAH with AU-chip accessing to the expression of serum protein fingerprinting, and Biomarker Wizard 3.1 software for analysis of test data, the data obtained from a preliminary statistical credits (calculated the mean X, P values and standard deviation of S), P <0.05 was considered statistically significant difference. We selected 5 proteins (p <0.0001) to establish intracranial aneurysm diagnostic model by the neural network from the serum protein fingerprint of a significant difference in the quality of m/z, and the other 35 samples (including aneurysm 20 cases , tSAH 15 cases) to verify it blindly. Results: 1. 410 peaks were totally detected from the samples, of which 371 proteins with statistically significant differences (p <0.05), and we use 5 specific mass peaks, which M / Z were 2980,3973,5917,6431,9232. (p <0.0001) to develop and train the ANN diagnostic model, 2. This model was blind tested and yeiled a sensitivity 90%, specificity 93.3%, positive predictive value of 94.1%, negative predictive value 87.5%. Conclusion: 1. Intracranial aneurysm and tSAH serum proteomics were significantly different. 2.The proteins which M / Z numbered 2980,3973,5917,6431,9232 may be the potential serum marker to establish prediction model for the intracranial aneurysm and it's the potential significance for screening the serum maker in intracranial aneurysm patients. 3. Intracranial aneurysms Spectrum of serum proteins may play an important role to explain the etiology and the molecular pathophysiological mechanisms of the intracranial aneurysms,.
Keywords/Search Tags:Intracranial aneurysm, SELDI-TOF-MS, artificial neural network, protein biomaker, subarachnoid hemorrhage
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