Extracellular Vesicle-Based Digital Scoring Assay for Detecting Early-stage Hepatocellular Carcinoma
基于细胞外囊泡的数字评分法检测早期肝细胞癌
基本信息
- 批准号:10560611
- 负责人:
- 金额:$ 63.28万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-01-18 至 2025-12-31
- 项目状态:未结题
- 来源:
- 关键词:AFP geneAbdomenAddressAlcoholic Liver DiseasesAntibodiesBioinformaticsBiologicalBiological AssayBiological MarkersBiologyBiometryCancer EtiologyCessation of lifeChemistryCirculationCirrhosisClinicalCouplesDevelopmentDevicesDiagnosisDiagnosticDisulfidesEarly DiagnosisEnsureEtiologyEvaluationExhibitsFiltrationGoalsHepatitis BHepatitis CImageInfectionJointsLiverLiver CirrhosisMediatingMedical centerMessenger RNAMethodsMicrofluidicsMinorModalityModelingMotivationNanostructuresNon-Invasive DetectionOncologyOperative Surgical ProceduresPatientsPerformancePhospholipidsPlasmaPopulationPrecipitationPrimary carcinoma of the liver cellsQuantitative EvaluationsRegimenReportingReproducibilityResearchResearch PersonnelReverse TranscriptionRiskRisk FactorsSamplingSecondary toSensitivity and SpecificitySerumSiteSolid NeoplasmSpecific qualifier valueSpecificitySpecimenSurfaceTechniquesTechnologyTrainingTumor-DerivedUltracentrifugationUltrasonographyValidationassay developmentcell typecohortdetection assaydiagnostic valuedigitalextracellular vesicleshepatocellular carcinoma cell linein-vitro diagnosticsinnovationmolecular pathologynanomaterialsneoplastic cellnon-alcoholic fatty liver diseaseparticlestandard of caretumor heterogeneityvesicular release
项目摘要
PROJECT SUMMARY
Extracellular vesicles (EVs) are a heterogeneous group of phospholipid bilayer-enclosed particles that are
released by all types of cells, and even more so by tumor cells. Since the biomolecular cargoes of tumor-
derived EVs mirror those of the parental tumor cells, characterizing tumor-derived EVs and profiling their cargo
are expected to be of substantial diagnostic value. Hepatocellular carcinoma (HCC), the fourth most common
cause of cancer-related deaths worldwide, most often develops in patients with underlying liver cirrhosis
secondary to alcoholic liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), or hepatitis B/C
infections. Cirrhosis from any cause is a well-established risk factor for HCC; however, current surveillance
regimens with abdominal imaging and serum biomarkers (e.g., AFP) have poor sensitivity for diagnosing HCC
at an early stage, when it is potentially curable. Therefore, biomarkers that sensitively distinguish early-stage
HCC from at-risk liver cirrhosis are desperately needed. Exploring the diagnostic potential of HCC EVs and EV
cargo profiling for detecting early-stage HCC holds great promise to significantly augment the ability of current
diagnostic modalities.
We propose an HCC EV digital scoring assay for detecting early-stage HCC, which couples two very powerful
technologies: EV Click Chip for purification of HCC EVs and reverse-transcription droplet digital PCR (RT-
ddPCR) for EV cargo profiling. One of the major challenges emerging in the field of EV utilization for clinical
use is the lack of robust and reproducible methods for the isolation of a pure tumor-derived EV population.
Conventional methods for isolating EVs, such as ultracentrifugation, filtration, and precipitation, are incapable
of discriminating tumor-derived EVs from non-tumor-derived EVs. New research efforts have been devoted to
exploring immunoaffinity-based capture techniques for enriching tumor-derived EVs in different solid tumors.
However, there are challenges identified for the single antibody-mediated tumor-derived EV enriching
approaches, such as limited sensitivity/specificity and a need for multiple capture antibodies to overcome the
tumor heterogeneity. The EV Click Chips can address these concerns with a 2-step covalent chemistry-based
tumor-derived EV purification (click chemistry-mediated EV capture/disulfide cleavage-driven EV release)
instead of antibody-mediated EV capture. The purified HCC EVs can then be characterized by quantifying a
panel of 20 HCC-specific mRNA markers by incorporating RT-ddPCR technology. The proposed research will
conduct: i) an exploratory development and optimization of the two functional components (i.e., EV Click Chip
and RT-ddPCR) and analytically validate the proposed HCC EV digital scoring assay, and ii) an evaluation of
the diagnostic performance of the proposed HCC EV digital scoring assay for detecting early-stage HCC using
training and validation cohorts. The long-term goal of this R01 proposal is to develop, optimize, and validate
the proposed HCC EV digital scoring assay for detecting early-stage HCC from at-risk liver cirrhotic patients.
项目总结
项目成果
期刊论文数量(0)
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Yazhen Zhu其他文献
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{{ truncateString('Yazhen Zhu', 18)}}的其他基金
Extracellular Vesicle-Based Digital Scoring Assay for Detecting Early-stage Hepatocellular Carcinoma
基于细胞外囊泡的数字评分法检测早期肝细胞癌
- 批准号:
10097789 - 财政年份:2021
- 资助金额:
$ 63.28万 - 项目类别:
Extracellular Vesicle-Based Digital Scoring Assay for Detecting Early-stage Hepatocellular Carcinoma
基于细胞外囊泡的数字评分法检测早期肝细胞癌
- 批准号:
10330444 - 财政年份:2021
- 资助金额:
$ 63.28万 - 项目类别:
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