Innovative RNA-Based Liquid Biopsy Detects Early Colorectal Cancer Accurately

In a groundbreaking development, researchers at the University of Chicago have unveiled a novel RNA-based liquid biopsy that demonstrates a remarkable 95% accuracy in detecting early-stage colorectal cancer. This advancement, reported in the 2025 study published in *Nature Biotechnology*, marks a significant leap forward in non-invasive cancer diagnostics, leveraging the analysis of RNA modifications rather than the traditional reliance on circulating cell-free DNA (cfDNA).

Liquid biopsies, which utilize a simple blood draw to identify cancer indicators, have garnered attention for their potential to transform cancer detection. However, existing methods have struggled with sensitivity, particularly in the early stages of disease when the concentration of cfDNA in the bloodstream is minimal. Dr. Chuan He, the senior author of the study and the John T. Wilson Distinguished Service Professor of Chemistry at the University of Chicago, emphasized the challenges posed by early diagnosis, stating, "You just don’t have enough tumor DNA released into the blood."

The innovative approach taken by Dr. He and his team involved focusing on circulating cell-free RNA (cfRNA) and examining RNA modification levels in blood samples from colorectal cancer patients. By shifting the focus from RNA abundance to the modifications present in RNA molecules, the researchers were able to achieve a more stable measure that could signal cancerous activity effectively. This method enhances the reliability of cancer detection, particularly at earlier stages when timely intervention can significantly impact patient outcomes.

The study involved collaboration with Dr. Marc Bissonnette, Associate Professor of Medicine at UChicago, who provided patient samples for analysis. The team's findings revealed not only modifications in cfRNA from human cells but also significant changes in RNA from gut microbiota, highlighting the interplay between cancer dynamics and microbial activity. Dr. He noted, "We found that RNA released from microbes has substantial differences between cancer patients versus healthy individuals."

The implications of this research extend beyond mere detection; it presents a new paradigm in understanding the biological interplay between cancer and the microbiome. As colorectal cancer rates continue to rise globally, with the World Health Organization reporting over 1.9 million new cases in 2020, this innovative approach could pave the way for earlier and more effective interventions.

Dr. He’s lab has previously focused on the biological functions of RNA modifications, and their new findings suggest that the activity of gut microbes significantly changes in response to tumor growth, further complicating the landscape of cancer diagnostics. Current tests that measure DNA or RNA abundance often fall short, particularly for early-stage cancer detection, with accuracy rates dropping below 50%. In contrast, this new RNA modification-based test shows nearly 95% accuracy overall, marking a substantial improvement over existing methodologies.

The potential for commercial application of this technology is promising, as it could lead to enhanced screening processes that prioritize early detection. The research was supported by several prestigious organizations, including the Ludwig Center for Metastasis at the University of Chicago and the National Institutes of Health, further underscoring the study's significance within the medical community.

In conclusion, the introduction of this RNA-based liquid biopsy not only represents a technological advancement in cancer detection but also illuminates the critical relationship between cancer and microbiome activity. As research in this area progresses, it is imperative to continue exploring the implications of RNA modifications as biomarkers for cancer, paving the way for more effective screening tools that could ultimately save lives.

Future studies are expected to expand on these findings, potentially leading to new diagnostics and treatment strategies that harness the power of RNA biology in cancer care. As the field of liquid biopsies continues to evolve, the integration of microbiome analysis may significantly enhance our understanding of cancer pathogenesis and improve patient outcomes in the years to come.