Researchers co-led by Ludwig Chicago’s Chuan He reported in a July Nature Biotechnology paper a method for profiling methylation patterns of cell-free (cf) RNA in plasma for the highly sensitive detection of colon cancer. One of the intrinsic limitations of cfDNA as a reporter of malignancy is that it is found at very low levels when cancers are in their earliest, and most manageable, stages of growth. This is less of a limitation with cfRNA. The method developed by Chuan and his colleagues, low-input multiple methylation sequencing, enables the detection and epigenetic analysis of diverse transfer RNAs and small noncoding RNAs derived from both the human genome and the microbiome. The researchers demonstrated that cfRNA derived from commensal gut bacteria is particularly useful for the detection of colon cancer by liquid biopsy. This is partly because inflammation around tumors remodels the local microbiome, and those changes are reflected in the altered patterns of chemical modifications seen in microbial cfRNA isolated from cancer patient plasma. Additionally, since bacteria turn over frequently, they release relatively large amounts of cfRNA into the bloodstream, greatly improving the sensitivity of detection. The researchers report that they could detect colorectal cancer in blood samples from patients with 95% accuracy even in the early stages of disease, when DNA-based liquid biopsies tend to miss the presence of tumors.
Modifications of microbiome-derived cell-free RNA in plasma discriminates colorectal cancer samples
Nature Biotechnology, 2025 July 8