Scientists have developed a liquid biopsy test that detects early-stage colorectal cancer with 95% accuracy by analyzing RNA modifications from gut bacteria circulating in blood.
The University of Chicago breakthrough could transform cancer screening by identifying the disease at its most treatable stages using a simple blood draw, potentially saving thousands of lives annually.
Unlike existing liquid biopsies that struggle with early detection, this approach leverages the dynamic relationship between tumors and the microbiome—the trillions of bacteria living in our digestive tract. When cancer develops, nearby gut bacteria respond by altering their cellular activity, leaving detectable molecular fingerprints in the bloodstream through modified RNA fragments.
Bacterial Signals Reveal Hidden Tumors
“That has been a major challenge for early diagnosis. You just don’t have enough tumor DNA released into the blood,” explained Chuan He, the John T. Wilson Distinguished Service Professor of Chemistry at UChicago and senior author of the study published in Nature Biotechnology. “That was a challenge for us and everyone else to do early diagnosis of colon cancer, so we decided to look at RNA instead.”
The research team discovered that gut bacteria release RNA fragments into the bloodstream that carry chemical modifications reflecting their metabolic state. In cancer patients, these bacterial RNA modifications change dramatically compared to healthy individuals, creating a unique molecular signature detectable through blood analysis.
Using a technique called LIME-seq (low-input multiple methylation sequencing), researchers analyzed blood samples from 27 colorectal cancer patients and 36 healthy controls. The method detected specific RNA modifications that act like molecular barcodes, revealing which bacteria are active and how they’re responding to nearby tumors.
Superior Performance Across Cancer Stages
The RNA modification-based test demonstrated remarkable accuracy across all disease stages:
- 95% overall accuracy in detecting colorectal cancer
- Maintained high sensitivity even for stage 0 and stage I cancers
- Significantly outperformed existing stool-based DNA tests (90% accuracy for late stages, below 50% for early stages)
- Surpassed FDA-approved blood tests measuring DNA methylation (~70% sensitivity)
The superior performance stems from the test’s unique approach to monitoring bacterial activity rather than tumor cell death. While traditional liquid biopsies depend on detecting DNA released when tumor cells die—a rare event in early cancer—this method captures the ongoing cellular conversations between tumors and their bacterial neighbors.
Microbiome Turmoil Signals Disease
Graduate student Cheng-Wei Ju and former postdoc Li-Sheng Zhang led the technical development, focusing on RNA modification patterns that remain stable regardless of sample timing or preparation. This consistency makes the test more reliable than approaches measuring simple RNA abundance, which can vary dramatically based on collection conditions.
“We found that RNA released from microbes has substantial differences between cancer patients versus healthy individuals,” He noted. “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.”
The bacterial population turnover also works in the test’s favor. Microbes reproduce and die much faster than human cells, constantly releasing fresh RNA fragments that reflect real-time gut conditions. This creates a continuous stream of molecular information about the local environment surrounding developing tumors.
From Laboratory to Clinic
Advanced machine learning analysis identified 12 key bacterial RNA modification sites that distinguish cancer patients from healthy individuals with exceptional accuracy. The algorithmic approach used support vector machines to create molecular classifiers capable of separating cancer signatures from normal variation.
Validation studies confirmed the test’s robustness across different patient populations and sample handling conditions. Blood samples remained stable for analysis up to 8 hours after collection, making the test practical for routine clinical use.
The research team has already begun exploring applications beyond colorectal cancer, with preliminary results suggesting the approach might detect pancreatic cancer and other malignancies that interact with the microbiome.
“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,” He emphasized. “Being able to detect the cancer at those early stages is unprecedented.”
The technology could ultimately complement existing screening methods while offering a less invasive alternative to colonoscopy for initial cancer detection, potentially increasing screening participation and catching more cancers when treatment is most effective.
ScienceBlog.com has no paywalls, no sponsored content, and no agenda beyond getting the science right. Every story here is written to inform, not to impress an advertiser or push a point of view.
Good science journalism takes time — reading the papers, checking the claims, finding researchers who can put findings in context. We do that work because we think it matters.
If you find this site useful, consider supporting it with a donation. Even a few dollars a month helps keep the coverage independent and free for everyone.