Liquid Biopsy Comparison Highlights Cell-Free RNA, Multiomic Approaches for Detecting Gastrointestinal Cancers (GenomeWeb)

This research, published in Cell Reports Medicine, explores the potential of circulating cell-free RNA (cfRNA) in blood plasma as a tool for detecting gastrointestinal cancers, comparing it with cell-free DNA (cfDNA) and highlighting the advantages of multiomic analyses. Here’s a summary of the key findings:

1. Study Overview: The study involved analyzing 161 blood plasma samples from individuals with colorectal cancer (CRC) or stomach adenocarcinoma, as well as samples from cancer-free individuals. The team compared various strategies including cfDNA whole-genome sequencing, cfDNA methylation, total cfRNA, and small cfRNA sequencing.
2. Multiomic Methods Prove More Informative: The research demonstrated that multiomic approaches, which combine different types of data like cfDNA methylation and cfRNA sequencing, were more informative for cancer detection than single-omics strategies.
3. Sensitivity of cfRNA: The study found that cfRNA-based variations provided a more sensitive view of the underlying cancers compared to cfDNA. There were considerable differences in the top genes recognized by cfDNA and cfRNA, indicating that these two modalities offer complementary insights when evaluated within plasma.
4. Pathway Alterations and Immune Signatures: cfRNA offered additional clues to the pathways altered in gastrointestinal cancers. The researchers observed changes in cancer-related immune signatures, such as T-cell and cancer-associated fibroblast scores, which were linked to cancer stage, prognostic patterns, and other features.
5. Potential for Personalized Treatment: The findings suggest that quantitative signatures and scores based on noninvasive biomarkers could help clinicians tailor therapeutic strategies to individual patients. Plasma sequencing data can provide targets for investigating mechanisms leading to different treatment responses.
6. Need for Further Exploration: The authors call for a more thorough exploration of cfRNAs in various extracellular vehicles and ribonucleoproteins. They emphasize that a full understanding of cell-free molecules requires a multifaceted approach incorporating various technological modalities and experimental paradigms.

This research underscores the potential of cfRNA in blood plasma as a sensitive and informative tool for the detection and monitoring of gastrointestinal cancers, offering new avenues for personalized cancer treatment and a deeper understanding of cancer biology.