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New technology for early detection of hepatocellular carcinoma

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Newswise — Primary liver cancer, the third leading cause of cancer-related deaths worldwide, claims more than 30,000 lives in the United States each year. The high mortality rate may be due in part to the fact that the majority of patients are discovered at a later stage. Unfortunately, today’s screening methods cannot routinely provide accurate and early detection.

A new study led by researchers at UCLA Jonsson Comprehensive Cancer Center and involving more than 50 investigators shows that a new technology under development can help treat early-stage hepatocellular carcinoma (HCC), which accounts for 80% to 85% of primary livers. This suggests that it may lead to a better way to detect . It usually occurs in patients with cirrhosis or chronic hepatitis B virus.

A technique under investigation measures and evaluates nanoparticles called extracellular vesicles (EVs). EVs are released from normal cells, but even more from tumor cells and cells within the tumor microenvironment.

“Tumor-associated extracellular vesicles are present in the circulation at relatively early stages of disease and are readily accessible at all disease stages,” says David Geffen, an investigator at UCLA Jonsson Comprehensive Cancer Center. said Hsian-Rong Tseng, an expert in molecular and medical pharmacology at UCLA School of Medicine. “EV cargo includes proteins, DNA, RNA, metabolites and lipids that reflect the tumor of origin, making EVs attractive for the development of cancer biomarkers. It is considered an emerging “liquid biopsy” strategy for invasive cancer detection. ”

Tseng and Vatche Agopian, Ph.D., a liver transplant surgeon and director of the Dumont UCLA Liver Cancer Center at the David Geffen School of Medicine, co-led the study with Yazhen Zhu, Ph.D., research pathologist and assistant professor of pathology and laboratory medicine. took the lead. Co-director of UCLA’s Liquid Biopsy Laboratory, he holds a Ph.D. from the David Geffen School of Medicine. They are co-first authors of a paper published in a peer-reviewed journal on 31 July. hepatology.

In this article, researchers and collaborators at UCLA presented a streamlined surface protein assay (HCC EV SPA) that can analyze and quantify eight subpopulations of HCC EVs. According to the authors, HCC EV SPA technology may one day enable rapid, sensitive and affordable detection of early-stage HCC in patients at risk of cirrhosis. It consists of two of his powerful platform technologies:

  • Proprietary “Click Beads” are used to purify HCC EVs from small plasma samples.
  • Multiplex, real-time immuno-PCR provides quantification of subpopulations of HCC EVs.

“From the resulting HCC EV SPA signature, we established a mathematical model to distinguish between early-stage cancer and cirrhosis,” said Zhu. “For this reason, we conducted a phase 2 biomarker study according to the International Liver Cancer Society’s biomarker development guidelines for the detection of early-stage HCC.”

The authors say they hope that early detection will allow doctors and patients to start treatment earlier, which will have a significant impact on survival.

“The prognosis for HCC is dismal, mainly because of the advanced stages in which the disease is often diagnosed,” Agopian said. “Although the American Association for the Study of Liver Disease (AASLD) guidelines recommend that at-risk patients undergo semi-annual liver ultrasounds to detect HCC at the healing stage, the accuracy of ultrasound imaging is limited. is still low, with a sensitivity between 60% and 70%, and a specificity of 90%.Clearly, the development of non-invasive tests for early detection is desperately needed.”

The authors noted that the impetus was bolstered by continued support from the National Institutes of Health (NIH), and the long-term goal of this particular research project, which is currently under consideration for new NIH funding, is to develop the HCC EV SPA. It is said that it is to be further optimized and verified. A large clinical study involving multiple institutions in the United States.


UCLA researchers Na Sun, Ceng Zhang, and Yi-Te Lee are co-first authors. In addition to the UCLA affiliation, Na Sun and her Ceng Zhang are visiting scholars from China.

Other UCLA authors are Benjamin Tran, Jing Wang, Hyoyong Kim, Junseok Lee, Ryan Zhang, Junhui Hu, Zhicheng Zhang, Kuan-Chu Hou, Hubert Tang, Tiffany Zhang, Icy Liang, Ziang Zhou, Mengxiang Chen, and Angela Hsiao. -I’m Jiun Yeh. , Wenyuan Lee, Shasmine Jasmine Chow, Helena Chang, Stephen Hui Han, Saeed Sadeghi, Richard Finn, Sammy Saab, Ronald Bustil, James Wu, Maduri Wadela, Myung-Shin Sim, Yunfeng Li, Hanlin Wang, Samuel French, Lily Wu, Vatche Agopian, Hsian-Rong Tseng, Yazhen Zhu.

Co-author Jasmine Wang is at UCLA and Cedars-Sinai Medical Center. Other Cedars-Sinai researchers include Manaf Alsudaney, Mazen Noureddin, Walid Ayoub, Alexander Kuo, Vinay Sundaram, Buraq Al-Ghaieb, Juvelyn Palomique, Kambiz Kosari, Irene Kim, Tsuyoshi Todo, Nicholas N. Nissen, Maria Lauda Tomasi is., Yoo Sung-yeon, Edwin M. Posadas, Sherry C. Lu, and Joo Dong-yang.

Vatche Agopian, Hsian-Rong Tseng, Yazhen Zhu, Ju Dong Yang, Renjun Pei, and Li Liang are all identified as corresponding authors.

Article: HCC EV ECG Score: Extracellular Vesicle-Based Protein Assay for Detection of Early Hepatocellular Carcinoma DOI: 10.1002/hep.32692