Microbial DNA Signature in Blood Plasma Differentiates Two Liver Cancer Types

Determining whether a cancerous tumor originated in a given location or spread from another organ is critical for guiding diagnosis and treatment decisions. When the primary tumor site cannot be identified, it becomes challenging to properly classify the malignancy and select the most effective therapy. Researchers have now found that a microbial DNA signature in blood plasma can distinguish primary liver cancer from colorectal cancer that has spread to the liver, offering a new pathway for diagnosis.

Scientists at the University of California San Diego (La Jolla, CA, USA) conducted a study to test whether microbial DNA could serve as a biomarker for differentiating cancer origins. They collected blood plasma samples from 16 patients with primary liver cancer and 11 patients with metastatic colorectal cancer. From these samples, they isolated cell-free DNA fragments—genetic material from dead cells found in bodily fluids—and performed metagenomic analysis to search for microbial patterns.

Image: Illustration of a cross-section of a blood vessel with red blood cells, white blood cells, and fragments of DNA (Photo Courtesy of UC San Diego/Adobe Firefly)

The analysis revealed that the microbial DNA classifier distinguished primary liver cancer from metastatic colorectal cancer with 90% accuracy. Specific species such as Pseudomonas aeruginosa, Corynebacterium accolens, and C. glucuronolyticum were enriched in primary liver cancer patients, while Acinetobacter tandoii, A. tianfuensis, A. septicus, A. parvus, Pseudomonas asiatica, and Bifidobacterium faecale were more common in patients with metastatic colorectal cancer. These microbial differences reflect distinct biological and immunological environments between the two cancer types.

Microbes found in primary liver cancer patients were often associated with immunocompromised conditions, liver transplant complications, and antimicrobial defense. In contrast, species enriched in metastatic colorectal cancer patients were linked to hospital-acquired infections, bloodstream infections, and gastrointestinal inflammation. The findings, published in eGastroenterology, provide evidence that microbial communities in the blood may carry diagnostic information about tumor origin. They also open possibilities for clinical applications such as non-invasive early cancer detection and monitoring of high-risk patients.

Additionally, the approach may aid cases where imaging results are unclear or unavailable, supporting more precise treatment planning. The researchers noted that this was one of the first studies to distinguish tumor origin using microbial DNA without the use of machine learning or artificial intelligence. In the future, microbial DNA-based biomarkers could guide cancer diagnosis and pave the way for microbiome-driven therapies. Larger studies will be needed to validate the findings and broaden their application.

“The use of microbial DNA signatures could open up a new diagnostic pathway, especially in situations where radiographic imaging is ambiguous or not accessible,” said Amir Zarrinpar, MD, PhD, professor in the Division of Gastroenterology & Hepatology at UC San Diego School of Medicine. “This is one of the first studies to show that microbial DNA in blood may be used to non-invasively distinguish tumor origin without the use of machine learning or artificial intelligence, particularly between two common liver pathologies.”

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