A New Approach to Early Cancer Detection Using RNA-Based Liquid Biopsies

Researchers at the University of Chicago have developed a more sensitive liquid biopsy that uses RNA instead of DNA to detect cancer. In their study, the new test identified the earliest stages of colorectal cancer with 95% accuracy, a significant improvement over current non-invasive methods.

The main challenge with early cancer diagnosis using standard liquid biopsies is the limited amount of circulating cell-free DNA (cfDNA) in the blood when tumors are still growing and thriving. “That has been a major challenge for early diagnosis. You just don't have enough tumor DNA released into the blood,” said Chuan He, senior author of the study published in Nature Biotechnology. To address this, the researchers shifted their focus to RNA.

Co-authors Cheng-Wei Ju and Li-Sheng Zhang explored the use of circulating cell-free RNA (cfRNA) for cancer detection. Instead of measuring the abundance of RNA, which can vary, the team analyzed chemical modifications on RNA molecules, which remain stable regardless of RNA quantity.

The researchers also discovered that they could detect RNA from gut microbes in the blood. The activity and RNA modifications of these microbes change in response to the presence of a tumor. “We found that RNA released from microbes has substantial differences between cancer patients versus healthy individuals,” Dr. He said. “In the gut when you have a tumor growing, the nearby microbiome must be reshaped in response to that inflammation. That affects the nearby microbes.”

Commercial tests measuring DNA or RNA in stool are about 90% accurate for later cancer stages but less than 50% for early stages. The new RNA modification-based test achieved nearly 95% accuracy, even at the earliest stages. “This is the first time RNA modifications have been used as a potential biomarker for cancer, and it looks to be much more reliable and sensitive compared to RNA abundance,” Dr. He added.