Researchers Discover New Nanoparticles in Blood That Could Transform Cancer Diagnosis

Scientists at the Icahn School of Medicine at Mount Sinai have identified a new class of RNAs bundled into tiny particles called extracellular vesicles (EVs) that could revolutionize the way cancer and other diseases are diagnosed. The team found that these molecules undergo changes in the presence of cancer, suggesting their potential as biomarkers for detecting prostate cancer or as drug targets. The work, led by Navneet Dogra, Ph.D., Edgar Gonzalez-Kozlova, Ph.D., Tzu-Yi Chen, Ph.D., and Gustavo Stolovitzky, Ph.D., was published in the August 16 online issue of Journal of extracellular vesicles.

Dr. Dogra is an Assistant Professor of Pathology, Molecular and Cellular Medicine and a member of the Icahn Genomics Institute, and Dr. Gonzalez-Kozlova is an Assistant Professor of Immunology, both at Icahn Mount Sinai. Dr. Chen, a former doctoral student in the laboratories of Dr. Dogra and Dr. Cordon-Cardo, is also affiliated with Pathology, Molecular and Cellular Medicine. Dr. Stolovitzky was previously an Assistant Professor at Icahn Mount Sinai and a research scientist at the IBM Watson Research Center in Yorktown Heights, New York.

The research team named these RNA molecules “EV-UGRs” (short for Extracellular Vesicles-Associated Unannotated Genomic Regions) after discovering them in the blood and urine of prostate cancer patients. UGRs are often called the “dark matter” of the human genome. They are thought to play a crucial role in controlling how genes are turned on and off and how genetic instructions are translated into proteins.

Extracellular vesicles and exosomes are tiny nanoparticles, about 1,000 times smaller than the thickness of a human hair, secreted by all cells into biological fluids such as blood and urine. These nanoparticles are known to carry genetic material, which is protected from the external environment. A collaboration between Dr. Dogra’s lab and Dr. Stolovitzky’s has discovered that EVs carry these previously unidentified bits of RNA dark matter.

“Until now, the RNA ‘dark matter’ associated with extracellular vesicles and exosomes has been largely overlooked. My team wanted to determine whether EV-UGRs could be useful for disease monitoring. We followed prostate cancer patients before and after surgery and were surprised to find that EV-UGR RNA expression changed after surgery. This is, to our knowledge, the first study to detail these ‘dark matter’ RNA molecules, EV-UGRs, in unprecedented detail in the context of prostate cancer,” said Dr. Dogra, lead author of the study. “Our results indicate that blood EV-UGRs undergo changes in the presence of cancer, suggesting a less invasive approach to diagnosing prostate cancer through simple liquid biopsies, potentially eliminating the need for more complex, painful, and infection-prone biopsy procedures.”

“Prostate cancer is a heterogeneous disease, often requiring only active surveillance rather than treatment. Our study uses novel RNA molecules associated with extracellular vesicles as a diagnostic tool. This technology offers significant potential for less invasive diagnostics and liquid biopsy in the near future,” said Ash Tewari, MD, MBBS, MCh, co-author and the Milton and Carroll Petrie Professor and Chair of the Department of Urology at Icahn Mount Sinai.

As part of their research, the researchers used next-generation small RNA sequencing to rapidly analyze human tissues and fluids. They also developed a cost-effective liquid biopsy test and created tools to isolate tiny EVs from blood and urine. Finally, they designed a computational pipeline to identify the new types of RNA.

According to Dr. Dogra, the EV-UGR discovery holds promise for noninvasive diagnosis not only of prostate cancer, but potentially other diseases as well. The researchers next plan to validate their findings through rigorous randomized clinical trials, which will test the new approach on a larger scale to confirm its effectiveness.

“This is a major and timely advance. The potential impact of this research is significant, promising a future where diseases like prostate cancer can be diagnosed quickly and less invasively. This advance could revolutionize care by reducing the time and discomfort associated with current diagnostic procedures, which could lead to earlier detection and more effective treatment strategies, improving patient outcomes and quality of life,” said co-author Carlos Cordon-Cardo, MD, PhD, the Irene Heinz Given and John LaPorte Given Professor of Pathology and Chair of the Department of Pathology, Molecular and Cellular Medicine at Icahn Mount Sinai.

The article is titled “Extracellular vesicles carry transcriptional ‘dark matter’ revealing tissue-specific information.”