1. HCC EV ECG score: An extracellular vesicle‐based protein assay for detection of early‐stage hepatocellular carcinoma
- Author
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Sun, Na, Zhang, Ceng, Lee, Yi‐Te, Tran, Benjamin V, Wang, Jing, Kim, Hyoyong, Lee, Junseok, Zhang, Ryan Y, Wang, Jasmine J, Hu, Junhui, Zhang, Zhicheng, Alsudaney, Manaf S, Hou, Kuan‐Chu, Tang, Hubert, Zhang, Tiffany X, Liang, Icy Y, Zhou, Ziang, Chen, Mengxiang, Yeh, Angela Hsiao‐Jiun, Li, Wenyuan, Zhou, Xianghong Jasmine, Chang, Helena R, Han, Steven‐Huy B, Sadeghi, Saeed, Finn, Richard S, Saab, Sammy, Busuttil, Ronald W, Noureddin, Mazen, Ayoub, Walid S, Kuo, Alexander, Sundaram, Vinay, Al‐Ghaieb, Buraq, Palomique, Juvelyn, Kosari, Kambiz, Kim, Irene K, Todo, Tsuyoshi, Nissen, Nicholas N, Tomasi, Maria Lauda, You, Sungyong, Posadas, Edwin M, Wu, James X, Wadehra, Madhuri, Sim, Myung‐Shin, Li, Yunfeng, Wang, Hanlin L, French, Samuel W, Lu, Shelly C, Wu, Lily, Pei, Renjun, Liang, Li, Yang, Ju Dong, Agopian, Vatche G, Tseng, Hsian‐Rong, and Zhu, Yazhen
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Liver Cancer ,Prevention ,Liver Disease ,Cancer ,Clinical Research ,Digestive Diseases ,Rare Diseases ,4.2 Evaluation of markers and technologies ,4.1 Discovery and preclinical testing of markers and technologies ,Detection ,screening and diagnosis ,Good Health and Well Being ,Humans ,Carcinoma ,Hepatocellular ,Liver Neoplasms ,Biomarkers ,Tumor ,Extracellular Vesicles ,Membrane Proteins ,Electrocardiography ,Glypicans ,Medical Biochemistry and Metabolomics ,Clinical Sciences ,Immunology ,Gastroenterology & Hepatology ,Clinical sciences - Abstract
Background and aimsThe 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 resultsTissue 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).ConclusionHCC EV ECG score demonstrated great potential for detecting early-stage HCC. It could augment current surveillance methods and improve patients' outcomes.
- Published
- 2023