The discovery that a specific kind of RNA in the blood can indicate the presence of cancer—and even pinpoint its location in the body—could lead to a simple blood test capable of catching many types of cancers in their earliest stages1.
There’s roughly a 40% chance that you will be diagnosed with cancer at some point during your life. The most critical aspect of that diagnosis is likely to be how advanced the cancer is—cancer caught early is usually treatable, but the prognosis becomes progressively poorer as the disease advances.
“Early detection of cancer has been shown to save lives,” says Daniel Kim, who is an assistant professor in biomolecular engineering at the University of California Santa Cruz and a visiting assistant professor in dermatology at the Stanford University School of Medicine in the USA. “And so we really want to be able to diagnose it early, before it spreads to other parts of the body.”
Currently, only four cancers have methods that are recommended for screening the general population in the USA, and they can be expensive or invasive. There is thus a great need for a simple test that can detect many different cancers before symptoms appear.
Kim and his team have been exploring the potential of measuring RNA in the blood to provide such a test, which is known as an RNA liquid biopsy.
Cancer cells constantly shed RNA, which then enters the bloodstream. Unlike DNA from cancer cells, which is rapidly degraded in blood, RNA is wrapped up in protective packages and hence remains largely intact. Thus, a simple blood test could be used to measure it.
Now, Kim and his team have discovered that RNA copied from repetitive sequences of DNA is particularly abundant in the blood of cancer patients. Furthermore, they have shown that it can even reveal the location of cancer cells.
“Repetitive RNAs are very robust biomarkers of cancer that are highly specific to cancer cells,” says Kim. “We were surprised that they provided such a robust signal.”
Conventional methods for sequencing RNA in the blood skip over repetitive RNAs. “Repetitive RNAs are typically discarded when looking at sequencing data,” notes Kim. And so his team has devised a method called COMPLETE-seq that can sequence and analyze both protein-coding and repetitive RNAs. They also employed machine learning to analyze the results.
The team found that cancers from different organs (including lung, colon, and esophagus) had different repetitive RNA signatures in the blood. They used this technique to detect pancreatic cancer, which has been dubbed a silent killer since it doesn’t produce symptoms until the late stages.
Kim is highly enthusiastic about the potential of their COMPLETE-seq RNA liquid-biopsy platform, and he envisions that it will soon be possible to take a simple blood test that can detect many different kinds of cancers in their earliest stages.
Reference:
1. Reggiardo, R. E. et al. Profiling of repetitive RNA sequences in the blood plasma of patients with cancer. Nature Biomedical Engineering (2023). https://doi.org/10.1038/s41551-023-01081-7
Daniel Kim, PhD, is an assistant professor in biomolecular engineering at the University of California Santa Cruz, a visiting assistant professor in dermatology at Stanford University School of Medicine, an associate member of the Canary Center at Stanford for Cancer Early Detection, and a research scholar of the American Cancer Society. His laboratory develops RNA technologies and tools for precision health, cancer early detection, and RNA medicine. His RNA research has been featured in Newsweek and by the director of the National Institutes of Health. It has also been recognized by awards from the Damon Runyon Cancer Research Foundation and the National Academy of Sciences.
