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Abstract Details
HCC EV ECG score: An extracellular vesicle-based protein assay for detection of early-stage hepatocellular carcinoma
Hepatology. 2023 Mar 1;77(3):774-788. doi: 10.1002/hep.32692. Epub 2023 Feb 17.
1California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
2Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics , University of Chinese Academy of Sciences, Chinese Academy of Sciences , Suzhou , People's Republic of China.
3Department of Pathology, Basic Medical College , Southern Medical University , Guangzhou , People's Republic of China.
4Department of Surgery, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.
5Division of Medical Oncology, Department of Medicine , Cedars-Sinai Medical Center , Los Angeles , California , USA.
6Department of Molecular and Medical Pharmacology , University of California, Los Angeles , Los Angeles , California , USA.
7Comprehensive Transplant Center , Cedars-Sinai Medical Center , Los Angeles , California , USA.
8Department of Medicine, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.
9Department of Pathology and Laboratory Medicine, Ronald Reagan Medical Center, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.
10Karsh Division of Gastroenterology and Hepatology , Cedars-Sinai Medical Center , Los Angeles , California , USA.
11Departments of Surgery and Biomedical Sciences , Cedars-Sinai Medical Center , Los Angeles , California , USA.
12Department of Medicine, Statistics Core, David Geffen School of Medicine , University of California, Los Angeles , Los Angeles , California , USA.
13Samuel Oschin Comprehensive Cancer Institute , Cedars-Sinai Medical Center , Los Angeles , California , USA.
14Department of Pathology, Nanfang Hospital and Basic Medical College , Southern Medical University , Guangzhou , People's Republic of China.
15Guangdong Province Key Laboratory of Molecular Tumor Pathology , Guangzhou , People's Republic of China.
16Jonsson Comprehensive Cancer Center , University of California, Los Angeles , Los Angeles , California , USA.
Abstract
Background and aims: The sensitivity of current surveillance methods for detecting early-stage hepatocellular carcinoma (HCC) is suboptimal. Extracellular vesicles (EVs) are promising circulating biomarkers for early cancer detection. In this study, we aim to develop an HCC EV-based surface protein assay for early detection of HCC.
Approach and results: Tissue microarray was used to evaluate four potential HCC-associated protein markers. An HCC EV surface protein assay, composed of covalent chemistry-mediated HCC EV purification and real-time immuno-polymerase chain reaction readouts, was developed and optimized for quantifying subpopulations of EVs. An HCC EV ECG score, calculated from the readouts of three HCC EV subpopulations ( E pCAM + CD63 + , C D147 + CD63 + , and G PC3 + CD63 + HCC EVs), was established for detecting early-stage HCC. A phase 2 biomarker study was conducted to evaluate the performance of ECG score in a training cohort ( n = 106) and an independent validation cohort ( n = 72).Overall, 99.7% of tissue microarray stained positive for at least one of the four HCC-associated protein markers (EpCAM, CD147, GPC3, and ASGPR1) that were subsequently validated in HCC EVs. In the training cohort, HCC EV ECG score demonstrated an area under the receiver operating curve (AUROC) of 0.95 (95% confidence interval [CI], 0.90-0.99) for distinguishing early-stage HCC from cirrhosis with a sensitivity of 91% and a specificity of 90%. The AUROCs of the HCC EV ECG score remained excellent in the validation cohort (0.93; 95% CI, 0.87-0.99) and in the subgroups by etiology (viral: 0.95; 95% CI, 0.90-1.00; nonviral: 0.94; 95% CI, 0.88-0.99).
Conclusion: HCC EV ECG score demonstrated great potential for detecting early-stage HCC. It could augment current surveillance methods and improve patients' outcomes.