Optimization of enrichment for MALDI TOF/TOF identification of cancer biomarkers

癌症生物标志物 MALDI TOF/TOF 鉴定的富集优化

• 批准号: 7286339
• 负责人: RADOSLAV GOLDMAN
• 金额: $ 7.54万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-13 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7286339
• 关键词: Aftercare; Biological Markers; Case-Control Studies; Chemoprevention; Chronic; Cirrhosis; Country; Detection; Diagnostic; Diagnostic Neoplasm Staging; Disease; Disease Management; Disease Progression; Early Diagnosis; Egypt; Epidemic; Experimental Designs; Goals; Health; Hepatitis B Virus; Hepatitis C; Hepatitis C virus; Incidence; Infection; Liver diseases; Malignant Conversion; Malignant Neoplasms; Maps; Mass Chromatography; Mass Spectrum Analysis; Methods; Molecular Weight; Patients; Peptides; Plasma; Population; Precancerous Conditions; Premalignant; Primary carcinoma of the liver cells; Proteins; Rate; Research; Risk; Sampling; Scheme; Screening for cancer; Screening procedure; Sensitivity and Specificity; Serum; Spectrometry; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Staging; Testing; Text; Time; Ultrafiltration; Virus Diseases; design; improved; interest; liquid chromatography mass spectrometry; magnetic beads; men; repository

DESCRIPTION (provided by applicant): Early detection of cancer and precancerous conditions improves patient survival. This study optimizes methods for discovery of a diagnostic set of peptides and proteins (P/P) in serum of patients with hepatocellular carcinoma (HCC). To identify biomarkers of HCC, we developed enrichment of low molecular weight (LMW) fraction of serum for matrix assisted laser desorption ionization-time of flight (MALDI- TOF/TOF) mass spectrometry (MS). This method allows high-throughput population screening as well as identification of the peptides of interest by TOF/TOF sequencing. We tested the biomarker discovery method on a pilot set of HCC cases and matched controls, which identified a set of P/P predictive of HCC with greater than 90% prediction accuracy. In this study, we propose to adjust the method to complementary enrichment using WCX and Cu-IMAC magnetic beads, expand the study to include a comparison with premalignant liver disease (150 cases, 150 matched controls, 50 cirrhosis), and to begin identification of the biomarker-candidates by sequencing. The samples come from our ongoing case-control study of HCC in Egypt, a country with an epidemic of hepatitis C infection and HCC. Our goal is to identify biomarkers that would improved early detection of HCC and track the natural progression of chronic viral infection to cancer. The identity of the biomarkers will be verified by MALDI-TOF/TOF sequencing and complementary liquid chromatography/mass spectrometry methods. Defining clinically applicable biomarkers of early-stage cancer has potentially far-reaching consequences for disease management and patient health. The biomarkers could be used to screen high risk populations for early signs of disease; to design and test improved chemoprevention strategies; and to follow disease progression after treatment. Identification of the P/P is expected to generate new hypotheses for targeted disease management.

描述（由申请人提供）：早期发现癌症和癌前状况可改善患者的生存。这项研究优化了在肝细胞癌（HCC）患者血清中发现一组肽和蛋白质（P/P）的方法。为了鉴定HCC的生物标志物，我们在基质辅助激光解吸时间（Maldi-Tof/TOF）质谱（MS）中开发了血清低分子量（LMW）的富集。该方法允许通过TOF/TOF测序鉴定高通量群体筛查以及鉴定感兴趣的肽。我们在一组HCC病例和匹配的控件的试验中测试了生物标志物发现方法，该方法鉴定了一组P/P的HCC预测，其预测准确性大于90％。在这项研究中，我们建议使用WCX和CU-IMAC磁珠来调整该方法以扩展研究，以包括与前肝病的比较（150例，150例，匹配的对照，50个ciRRHOSIS），并开始通过测序鉴定生物标记剂。这些样本来自我们正在进行的埃及HCC病例对照研究，埃及是一个患有丙型肝炎感染和HCC的国家。我们的目标是确定可以改善HCC早期检测并跟踪慢性病毒感染对癌症的自然发展的生物标志物。生物标志物的身份将通过MALDI-TOF/TOF测序和互补的液相色谱/质谱法验证。定义临床适用的早期癌症生物标志物可能对疾病管理和患者健康产生深远的影响。这些生物标志物可用于筛查高风险种群，以实现早期疾病迹象。设计和测试改进的化学预防策略；并在治疗后跟随疾病进展。 P/P的鉴定有望为有针对性的疾病管理产生新的假设。

项目成果

Detection of hepatocellular carcinoma using glycomic analysis.

• DOI: 10.1158/1078-0432.ccr-07-5261
• 发表时间: 2009-03-01
• 期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
• 作者: Goldman R;Ressom HW;Varghese RS;Goldman L;Bascug G;Loffredo CA;Abdel-Hamid M;Gouda I;Ezzat S;Kyselova Z;Mechref Y;Novotny MV
• 通讯作者: Novotny MV

Analysis of MALDI-TOF mass spectrometry data for detection of glycan biomarkers.

分析 MALDI-TOF 质谱数据以检测聚糖生物标志物。

• 发表时间: 2008
• 期刊: Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing
• 作者: Ressom,HabtomW;Varghese,RencyS;Goldman,Lenka;Loffredo,ChristopherA;Abdel-Hamid,Mohamed;Kyselova,Zuzana;Mechref,Yehia;Novotny,Milos;Goldman,Radoslav
• 通讯作者: Goldman,Radoslav