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Principal Investigator: HSIAN-RONG TSENG
Organization: UNIVERSITY OF CALIFORNIA LOS ANGELES
Fiscal Year: 2024
Award: $195,726
Funding agency: National Cancer Institute
PROJECT SUMMARY/ABSTRACT
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Local regional
therapies, such as local ablation and transarterial chemoembolization (TACE), are the most commonly used
treatment modality for HCC. Following treatment, patients undergo radiologic imaging for evaluation of treatment
response. Assessing treatment response to local regional therapies is often challenging due to treatment-related
nonspecific changes and definitive assessment typically requires repeated cross-sectional imaging. Similarly,
there is poor radiologic-histological correlation of post-treatment tumor viability, with discordant results seen in
38% of HCC patients after local regional therapies. While serum alpha-fetoprotein (AFP) can aid to assess
treatment response, less than half of all patients with HCC have an elevated AFP before treatment. This limits
its utility for broader implementation.
Extracellular vesicles (EVs) are phospholipid bilayer-enclosed particles released by both normal and tumor cells.
Compared to other types of liquid biopsy, EVs have advantages in their higher frequency in circulation and the
simplicity of sample preservation. One major challenge of this approach, however, is that tumor-derived EVs
typically co-exist with those from non-tumor sources, resulting in complex background signals. To overcome this
technical barrier for selective purification of tumor-derived EVs, our joint research team developed a novel
nanotechnology platform named EV Click Chip with the support of NIH/NCI R01 funding (R01 CA253651). When
used in combination with reverse-transcription droplet digital PCR (RT-ddPCR), this HCC EV Digital Scoring
Assay (EV Click Chip + RT-ddPCR) is able to purify HCC EVs and quantify HCC-specific mRNA signatures from
the purified HCC EVs. We recently showed this assay can distinguish early-stage HCC from liver cirrhosis with
an area under the receiver operating characteristic curve (AUROC) of 0.93. Given the potential of HCC EV Digital
Scoring Assay for reflecting the presence of HCC and tumor burden, we hypothesized it could be used for
evaluating treatment response in HCC patients receiving locoregional therapies. The study aims of this two-year
R01 revision application are to investigate the performance of HCC EV Digital Scoring Assay (EV Click Chip +
RT-ddPCR) for evaluation of HCC treatment response to local ablation or TACE.
Terms: <Ablation><After Care><After-Treatment><Aftercare><Alpha-1-Fetoprotein><Alpha-Fetoglobulin><Area><Assay><Bioassay><Biological Assay><Biological Markers><Biometrics><Biometry><Biostatistics><Blood Plasma><Blood Serum><Cancer Cause><Cancer Etiology><Cell Communication and Signaling><Cell Signaling><Cessation of life><Chemoembolization><Chemotherapy Embolization><Circulation><Clinical><Complement><Complement Proteins><Complex><Death><Early Diagnosis><Enrollment><Evaluation><Fetuins><Frequencies><Funding><Future><General Radiology><Hepatic><Hepatic Cirrhosis><Hepatocarcinoma><Hepatocellular Carcinoma><Hepatocellular cancer><Hepatoma><Histologic><Histologically><Image><Image Analyses><Image Analysis><Intracellular Communication and Signaling><Joints><Liver Cells Carcinoma><Liver Cirrhosis><Logistic Regressions><Measures><Medical center><Messenger RNA><Microfluidics><Modality><Modeling><Motivation><NIH><Names><Nanoplatform><Nanotechnological platform><National Institutes of Health><Normal Cell><Oncology><Oncology Cancer><Patients><Performance><Phase><Phosphatides><Phospholipids><Plasma><Plasma Serum><Primary carcinoma of the liver cells><Process><ROC Analyses><ROC Curve><Radiography><Radiology><Radiology Specialty><Research><Reticuloendothelial System, Serum, Plasma><Reverse Transcription><Roentgenography><Sampling><Serum><Signal Transduction><Signal Transduction Systems><Signaling><Source><Testing><Training><Translations><Tumor Burden><Tumor Cell><Tumor Load><Tumor-Derived><United States National Institutes of Health><Validation><assay development><bio-markers><biologic marker><biological signal transduction><biomarker><case control><case-controlled><cohort><complementation><digital><early detection><enroll><extracellular vesicles><image evaluation><image interpretation><imaging><in-vitro diagnostics><liquid biopsy><liver carcinoma><mRNA><molecular pathology><name><named><naming><nanomaterials><nanotechnology platform><neoplastic cell><novel><particle><post treatment><preservation><prevent><preventing><radiologic imaging><radiological imaging><receiver operating characteristic analyses><receiver operating characteristic curve><response to therapy><response to treatment><therapeutic response><therapy response><translation><treatment response><treatment responsiveness><tumor><validations><µfluidic><α-Fetoproteins>