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Screening Of Serum Differential Protein In ARHL Susceptible Individuals

Posted on:2017-03-29Degree:MasterType:Thesis
Country:ChinaCandidate:C L JiangFull Text:PDF
GTID:2284330503463420Subject:Otolaryngology science
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Objective:ARHL is the most common sensory impairment in the elderly. It has become the primary factor in hearing disability. The etiology is still unknown. In this study, proteomic technique was used to study the changes of peripheral serum protein expression in ARHL susceptible individuals. The differentially expressed proteins were screened. The pathogenesis of ARHL was further explored and the susceptible individual screening strategy was studied. Methods:1. Hospitalized patients without ear diseases from January 2015 to November 2015 were selected. Pure tone audiometry and questionnaire were conducted(n=78).According to which the Z score of every patient was calculated, the patients were divided into susceptible group(n=52) and unsusceptible group(n=26);2. Venous blood was drawn out from the patients and the serum was separated. Then the weak cation was used to extract the peptide. The differentially expressed peptides in the serum of ARHL susceptible individuals were screened by MALDI-TOF MS and BE software. Differentially expressed polypeptides were selected to establish the diagnostic model. The model was validated by blind method using the validation group serum samples. Results:1. There were 78 people met the inclusion criteria, including 52 cases in susceptible group and 26 cases in unsusceptible one. There were 39 males and 39 females with a mean age of 71.23 + 7.61 years ranging from 60-86 years. The susceptible group included 19 males and 33 females with the an average age of 71.5 + 7.85 years. The unsusceptible group included 20 males and 6 females with an average age of 70.69 + 7.23 years.2. Nine polypeptides of statistical significance were found. Their molecular weight was 4047.1 Da, 2957.1 Da, 4084.5 Da, 4260.1 Da, 2102.9 Da, 1288 Da, 3276 Da, 4146.2 Da and 3153.4 Da respectively. Among these polypeptides peaks, there were 6 up regulated and 3 down regulated.3. The diagnostic model of serum protein finger print of ARHL susceptible individual was established by using 2 differentially expressed protein which had the best modeling effect(molecular weight was 3276.0Da and 3153.4Da).The sensitivity and specificity of the model were 68.18% and 66.67% respectively by the blind verification test. And the area under the ROC curve was 0.711823. Conclusion:1. Z value method can be used to distinguish ARHL susceptible individuals from unsusceptible individuals objectively.2. There was a significant difference in the serum protein fingerprint between ARHL susceptible group and unsusceptible one.3. It was the first time to use the weak cation exchange beads and MALDI-TOF MS technique to study serum differentially expressed protein of ARHL susceptible individual. Nine significantly differentially expressed polypeptides were found.4. The first serum protein fingerprint diagnostic model was firstly established for ARHL susceptible individual. The results of blind verification test showed that this model had a certain recognition ability to tell the ARHL susceptible individuals apart from unsusceptible ones.5. In this study, we explored the pathogenesis of ARHL and the methods of screening its susceptible individuals from the levels of protein and peptide. This study also provided reference for searching better prophylactic-therapeutic measures of ARHL.
Keywords/Search Tags:Presbycusis, Disease susceptibility, Proteomics, Mass spectrometry
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