Simple Blood Test Offers Non-Invasive Alternative for Early Colon Cancer Detection

Colorectal cancer remains one of the leading causes of cancer-related deaths, and early detection is critical for improving patient outcomes. Current methods, such as colonoscopy, are effective but invasive and often face low compliance rates. Now, a new blood-based diagnostic strategy aims to overcome these limitations by offering a non-invasive approach that identifies cancer-associated signals earlier and with greater convenience.

Researchers from the Robert H. Lurie Comprehensive Cancer Center of Northwestern University (Chicago, IL, USA) have developed a technique called LIME-seq (Low-Input Multiple Methylation Sequencing), which can detect RNA modifications at nucleotide resolution across diverse RNA species. Unlike commercial kits, which often fail to capture short RNA molecules, such as tRNAs, or map RNA methylations, this method preserves and analyzes these key signals. The system uses HIV reverse transcriptase to create complementary DNA from cell-free RNA, ensuring a comprehensive capture of RNA species in blood plasma.

The study, published in Nature Biotechnology, revealed that tRNAs are a major component of cell-free RNA in plasma. LIME-seq was able to identify both human RNA-derived signals and microbial genome-derived signals, providing a richer picture of molecular changes associated with cancer. Importantly, the method could track RNA methylation changes, a promising biomarker for tumor development.

In tests comparing plasma samples from 27 colon cancer patients with those from 36 healthy individuals, researchers found clear methylation differences between the groups. These findings suggest that methylation changes in microbiome-derived cell-free RNA may reflect tumor microenvironment activity, offering heightened sensitivity for early cancer detection.

The potential applications of this approach are significant. By evaluating host and microbiome RNA signals, LIME-seq could help identify colorectal cancer at its earliest stages, when curative surgery is most effective. Researchers emphasize the need for larger clinical studies to validate these biomarkers and expand the method’s use to other cancers, potentially revolutionizing non-invasive cancer screening.

“The new LIME-seq represents a revolutionary approach that opens up opportunities to explore cell-free RNA in cancer biomarker discovery,” said Wei Zhang, co-author of the study. “This is especially exciting for colorectal cancer detection because this new method would allow us to evaluate the potential of early cancer detection through monitoring the dynamic status of host microbiome, which, compared to mutational signals, are more likely to reflect early signs of cancer development.”

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Robert H. Lurie Comprehensive Cancer Center of Northwestern University