Blood microbial DNA distinguishes liver cancer from metastatic lesions

A simple blood test analyzing microbial DNA could help doctors tell apart primary liver cancer from colorectal cancer that has spread to the liver, according to a new study in eGastroenterology.

Researchers used shotgun metagenomic sequencing on blood plasma and tumor tissue samples from patients with hepatocellular carcinoma (HCC) and metastatic colorectal cancer (mCRC). They found that microbial DNA circulating in the blood provided stronger diagnostic signals than tissue-based profiling, revealing distinct bacterial “fingerprints” for each cancer type.

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In the study, plasma samples clearly separated HCC from mCRC, while tumor tissues did not. Specific bacterial groups—including Pseudomonas aeruginosa in HCC and Acinetobacter species in mCRC—emerged as potential biomarkers.

Powerful tool

“Blood-derived microbial DNA captures signals from across the body, not just a single lesion,” said Professor Amir Zarrinpar. “This makes it a powerful, non-invasive tool for distinguishing liver cancers that often look similar on imaging scans.”

If validated in larger studies, microbial cfDNA profiling could:

• Improve accuracy when imaging results are inconclusive
• Complement existing biomarkers like alpha-fetoprotein (AFP)
• Enable earlier detection in high-risk patients with cirrhosis
• Inform treatment choices, from surgery to systemic therapy

This pioneering study demonstrates that blood microbial cfDNA can distinguish hepatocellular carcinoma from metastatic colorectal cancer in the liver. By identifying distinct microbial taxa associated with each tumor type, the research lays critical groundwork for non-invasive, microbiome-based diagnostics.

Although not yet ready for clinical use, these findings point toward a future where the microbiome becomes a powerful ally in oncology, aiding in cancer detection, prognosis, and potentially guiding therapy. As sequencing costs decline and validation studies expand, microbial cfDNA may soon join the frontline of precision cancer medicine.