Proteomic Analysis of Serum in Liver Cancer

肝癌血清的蛋白质组学分析

基本信息

批准号：
7774370
负责人：
RADOSLAV GOLDMAN
金额：
$ 34.61万
依托单位：
GEORGETOWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-02-15 至 2012-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7774370
关键词：
Aftercare Age Biological Assay Biological Markers Chemoprevention Chromatography Chronic viral hepatitis Cirrhosis Classification Collaborations Country Diagnostic Diagnostic Neoplasm Staging Disease Disease Management Disease Progression Early Detection Research Network Early Diagnosis Egypt Enzyme-Linked Immunosorbent Assay Epidemic Experimental Designs Gender Goals Health Hepatitis C Isotopes Label Laboratories Liver Cirrhosis MALDI-TOF Mass Spectrometry Malignant Conversion Malignant Neoplasms Malignant neoplasm of liver Mass Spectrum Analysis Methods Molecular Weight Newly Diagnosed Patients Peptide Synthesis Peptides Performance Pilot Projects Plasma Population Precancerous Conditions Primary carcinoma of the liver cells Proteins Proteomics Sampling Scheme Screening for cancer Sensitivity and Specificity Serum Serum Proteins Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Staging Testing Text Time Ultrafiltration Validation Virus Diseases case control design high risk high throughput screening improved interest liquid chromatography mass spectrometry magnetic beads performance tests protein aminoacid sequence reversed phase chromatography

项目摘要

DESCRIPTION (provided by applicant): Early detection of cancer and precancerous conditions improves patient survival. This study will identify a set of peptides and proteins (P/P) in serum associated with hepatocellular carcinoma (HCC). To achieve this goal, we developed enrichment of the low molecular weight (LMW) serum fraction for matrix assisted laser desorption ionization-time of flight (MALD1-TOF/TOF) mass spectrometric (MS) identification of biomarkers. This method allows high-throughput screening of a population 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 from our unique study of HCC in Egypt, a country with an epidemic of hepatitis C viral infection. The pilot-study identified a set of six peptides that predict HCC with 96% prediction accuracy. In this study, we propose to expand the project and focus on identification of peptides associated with malignant conversion of liver cirrhosis. Our goal is to identify biomarkers that would improve early detection of HCC in this high-risk group and track the natural progression of chronic viral hepatitis to cancer. We will cross validate our ongoing study in Egypt with a study of HCC in the US population; verify peptide- identification by MALDI-TOF/TOF sequencing, complementary liquid chromatography/mass spectrometry, synthesis of peptides standards, and immunodepletion; develop improved methods for quantification of the peptides; and test performance of the biomarker-candidates. 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 new 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。这项研究将确定与肝细胞癌（HCC）相关的血清中的一组肽和蛋白质（P/P）。为了实现这一目标，我们开发了用于基质辅助激光解吸时间（MALD1-TOF/TOF/TOF）质谱（MS）质谱（MS）鉴定生物标志的低分子量（LMW）血清分数的富集。该方法允许对人群进行高通量筛查以及通过TOF/TOF测序鉴定感兴趣的肽。我们在一组HCC病例的试验中测试了生物标志物发现方法，并匹配了我们对埃及HCC的独特研究的控制，这是一个患有丙型肝炎病毒感染的国家。试验研究确定了一组六个肽，这些肽预测HCC的预测准确性为96％。在这项研究中，我们建议扩大项目，并专注于鉴定与肝硬化的恶性转化有关的肽。我们的目标是鉴定生物标志物可以改善这个高风险群体中HCC的早期检测，并跟踪慢性病毒肝炎对癌症的自然发展。我们将通过对美国人口中的HCC进行研究来跨越埃及正在进行的研究；通过MALDI-TOF/TOF测序，互补液相色谱/质谱，肽标准标准的合成和免疫序列来验证肽鉴定；开发改进的定量肽的方法；和生物标志物候选物的测试性能。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。设计和测试新的化学预防策略；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

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Semi-automated identification of N-Glycopeptides by hydrophilic interaction chromatography, nano-reverse-phase LC-MS/MS, and glycan database search.

DOI：
10.1021/pr201183w
发表时间：
2012-03-02
期刊：
Journal of proteome research
影响因子：
4.4
作者：
Pompach P;Chandler KB;Lan R;Edwards N;Goldman R
通讯作者：
Goldman R

LC-MS/MS-PRM Quantification of IgG glycoforms using stable isotope labeled IgG1 Fc glycopeptide standard.

使用稳定同位素标记的 IgG1 Fc 糖肽标准品对 IgG 糖型进行 LC-MS/MS-PRM 定量。

DOI：
10.1101/2022.08.02.501850
发表时间：
2022
期刊：
bioRxiv : the preprint server for biology
影响因子：
0
作者：
Sanda,Miloslav;Yang,Qiang;Zong,Guanghui;Chen,He;Zheng,Zhihao;Dhani,Harmeet;Khan,Khalid;Kroemer,Alexander;Wang,Lai-Xi;Goldman,Radoslav
通讯作者：
Goldman,Radoslav

Decreased risk of squamous cell carcinoma of the head and neck in users of nonsteroidal anti-inflammatory drugs.