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The Detection and Significance of Serum Protein Markers in Nephroblastoma of Children

Author: ZhangZuo
Tutor: WangJiaXiang
School: Zhengzhou University
Course: Pediatric surgery
Keywords: Wilms tumor Diagnosis Support Vector Machine Protein fingerprint SELDI-TOF-MS
CLC: R737.11
Type: Master's thesis
Year: 2007
Downloads: 69
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Abstract

Research background Wilms tumor (nephroblastoma), also known as embryonic kidney tumor, wilms tumor (WT), children, the most common solid tumor in the retroperitoneal. Since the 1990s, the tumor resection rate nearly 100.0%, 5-year survival rate of 80.0%. Wilms tumor congenital disease, age of onset, the children have their own characteristics can not be timely and accurate perception of the disease, and the current world-wide lack of effective means of early detection, the existing B ultrasonography, CT, intravenous the pelvis according shadow (IVP) check means only when the tumor grows to a certain size in order to be found is still unable to meet the clinical noninvasive, simple, efficient and rapid early diagnosis requirements. Clinical needs good specificity, high sensitivity, non-invasive, less painful tumor markers, especially the establishment of serum markers of R \u0026 D and its corresponding inspection methods. Development of proteomics for cancer diagnosis provides a new way of thinking and technology platform. In this study, proteomics surface enhanced laser desorption ionization - time of flight mass spectrometry (Surface Enhanced Laser Desorption the / Ionizayion Time of Flight Mass Spectrometry, SELDI-TOF-MS) technology and bioinformatics methods to analyze Wilms tumor suffering children, differentially expressed proteins in the serum of other pediatric abdominal cavity in children with solid tumors and normal children, screened specific protein markers to investigate serum protein fingerprint model for the early diagnosis of Wilms tumor, to create highly specific and sensitive sexual Wilms tumor diagnostic model, as well as the evaluation of the model of Wilms tumor diagnostic value. Research purposes to detect Wilms tumor in children with serum proteins, to filter specific protein markers, serum protein fingerprint model building for early diagnosis and differential diagnosis of Wilms tumor, and explore the serum protein pattern model based on support vector machine Wilms tumor diagnostic applications. Materials and methods. Materials 1.1 75 serum samples of the specimens: 30 cases of Wilms' tumor, 25 cases of other abdominal solid tumors (9 cases of neuroblastoma, hepatoblastoma, pancreatic neuroblastoma cases of retroperitoneal malignant teratogenic tumor in 5 cases, 3 cases of rhabdomyosarcoma, adrenocortical carcinoma cases), 20 cases of normal control group. All malignant specimens were confirmed by pathology. Wilms' tumor group, 16 males and 14 females, mean age 2.8 ± 0.1 years. Other pediatric abdominal solid tumor group, 11 males and 14 females, mean age 3.5 ± 0.1 years. Normal control group with Wilms tumor age and sex-matched. 1.2 devices surface-enhanced laser desorption ionization - time of flight mass spectrometry (Surface Enhanced Laser Desorption / Ionization Time of Flight Mass Spectrometry, SELDI-TOF-MS), PBS Ⅱ ~~ Ciphergen Inc.. USA). The main parameters: the collection range from 1000 to 50000; optimized range 2000-30000.1.3 chip weak cation exchange (WCX2) protein chip. 1.4 application software and markers evaluation application software: Proteinchip Software 3.1, Biomarker Wizard and ZUCI-ProteinChip Data Analyze System package. Support vector machine (SVM): MATLAB6.50SU-SVM toolbox. Indicators of evaluation experiments: sensitivity, specificity, Youden index. 2. Method of 2.1 serum sample processing: U9 solution treatment serum samples thawed in the ice bath the diluted in 100Mm NaNC (pH = 4), and Bioprocessor pretreatment WCX2 of protein chip binding reaction 60 min, above NaNC buffer cleaning chip point 50% saturated SPA solution after removing the chip air-dried, machine-readable chip. 2.2SELDI operation: SELDI mass spectrometer to complete the set, recording the mass spectra of each case samples of serum proteins. The original correction data using Proteinchip Software 3.1 homogenization of the total ion intensity and molecular weight. Noise filter using Biomarker Wizard and ZUCI-ProteinChip Data Analyze System package, local extreme method finds the sample each peak, and filter the signal-to-noise ratio is less than 2 peak, 10% minimum threshold cluster analysis, the preliminary screening results. 2.3 serum sample groups: group 1. The pediatric abdominal solid tumor group and normal control group, Group 2. Wilms tumor group and the normal control group, group 3. Wilms tumor group and other abdominal solid tumors in children 2.4 modeling method: preliminary screening out mass-to-charge ratio of peak to do Wilconxon rank sum test, screening each significant m / z values. There will be significant differences in m / z value data input support vector machine further analysis, discriminant model using the training set to test the effectiveness of the model of the test set, the filter for modeling the m / z-values. The sensitivity and specificity of the evaluation model. Results 1. 521 m / z peak after preliminary filtration screening abdominal solid tumors in children tumor mass spectral data of the group and the normal control group tumor group and normal control group, their relative intensity to do Wilconxon rank sum test analysis P values ??less than 0.01 m / z peak 11 from the significant difference in any combination of the protein peaks, using the the SVM filter out the predictive value index youden highest combination of model, weed out the m / z 3 located 4656.5,5643.1 and 7777.4 protein markers in the tumor group high expression, and low expression in normal control group. Potential markers as the union of two input values, leave-one-crossing detection discriminant model on the test set specificity of 100.0%, a sensitivity of 96.3%. 2. After the initial filter screening Wilms tumor mass spectral data of the group and the normal control group Wilms tumor group and normal control group 352 M / Z peak, do Wilconxon rank sum test analysis of their relative intensity P values ??less than 0.01 M / Z peak 11 from differences significantly with any combination of the protein peak of, using SVM screening the predictive value of youden index the highest combination model, sieve the m / z located 6984.5 and 6455.5 of the protein marker substance 2 in Wilms cell tumor of the group low expression and high expression in the normal control group. Potential markers as the union of two input values, leave-one-crossing detection discriminant model on the test set specificity of 100.0%, a sensitivity of 100.0%. 3. The initial screening of Wilms 'tumor group and other abdominal solid tumors in children with Wilms' tumor group and other pediatric celiac solid tumors group of 352 M / Z peak by the Wilconxon rank sum test analysis P values ??less than 0.01 M / Z The peak 7 Ge from differences significant protein peaks of any combination, using SVM screening the predictive value of youden index the highest combination of model and sieve out the m / z located 6914.0 and 3256.7 of the protein marker substance two, Wilms cell tumor group high expression, low expression group in other abdominal solid tumors in children. Potential markers as the union of two input values, using leave-one the classifier evaluation model prediction, discriminant model on the test set specificity of 100.0%, sensitivity of 93.3%. Conclusion surface-enhanced laser desorption ionization time-of-flight mass spectrometry combined with support vector machine the Wilms tumor serum protein fingerprint model is established early diagnosis of a Wilms tumor specificity, the new method with high sensitivity for tumors in children large-scale screening, differential diagnosis and qualitative diagnosis of children with Wilms' tumor.

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