Colorectal Cancer Reveals Unique Microbial Fingerprint, Offering New Diagnostic and Prognostic Insights

Scientists have discovered that colorectal cancer (CRC) carries a distinct microbial “fingerprint,” setting it apart from other cancers. Researchers found that only colorectal tumors consistently harbor unique microbial communities, challenging the long-held belief that all cancers do. This discovery could lead to more precise diagnoses, improved risk stratification, and potentially new therapeutic strategies.

Mining Microbial DNA from Cancer Genome Sequencing

Cancer genome sequencing, designed to read human DNA, also captures traces of microbial DNA present in samples. A recent study from the University of East Anglia (UEA) demonstrated that these microbial traces are particularly revealing in colorectal cancer. The research team developed computer programs to remove human DNA and analyze the remaining microbial DNA, correlating this information with clinical data from patients.

Challenging the Universal Microbial Signature Theory

The analysis, which drew on whole genome sequencing (WGS) data from more than 9,000 cancer patients and Genomics England DNA sequence information from 11,735 cancer samples spanning 22 cancer types, pushes back against the idea that every cancer type has a distinct microbiological signature. “What we found challenges previous claims that each cancer type has a distinct microbiological signature or fingerprint,” said lead researcher Dr. Abraham Gihawi, from UEA’s Norwich Medical School.

Specificity of Microbial Signatures in Colorectal Cancer

The colon’s microbe-dense environment makes it a plausible location for tumor tissue to carry a consistent microbial pattern. The study’s results showed that only colorectal tumors possess distinctly identifiable microbial communities. “Our results show that only colorectal tumors possess distinctly identifiable microbial communities,” Dr. Gihawi stated. “We found that these microbial signatures were so specific that they could accurately distinguish colorectal tumors from other tumors.”

Potential Diagnostic and Prognostic Applications

This specificity could be valuable in challenging diagnostic situations, such as determining the origin of metastatic tumors or interpreting ambiguous biopsy samples. Researchers hope this could help doctors diagnose the disease more precisely and provide new avenues for research into the microbes found in colorectal cancer.

Beyond Colorectal Cancer: Insights into Oral Cancer and Sarcomas

The sequencing-based approach also flagged clinically relevant viruses in other cancers, including oral cancers. The study accurately detected human papillomavirus (HPV), which influences clinical classification and treatment decisions. The team detected Human T-Lymphotropic Virus-1 (HTLV-1), a rare virus linked to certain cancers, potentially leading to earlier diagnoses.

the analysis connected microbial signals to patient outcomes in some sarcoma cases. Certain bacteria were associated with poorer survival rates, while others were linked to better survival rates, suggesting a potential role for microbes in refining prognosis and guiding treatment strategies.

The Growing Clinical Value of Whole Genome Sequencing

Prof Daniel Brewer, from UEA’s Norwich Medical School, emphasized the growing clinical value of whole genome sequencing in identifying pathogenic organisms like HTLV-1 and papillomavirus, which might otherwise go undetected. “By revealing these hidden infections and providing insight into cancer prognosis – particularly in sarcomas – it demonstrates how genomic analysis is becoming an indispensable tool in precision medicine,” he said.

The findings also suggest that oral cancer, in some cases, may be a close diagnostic consideration, further emphasizing the importance of comprehensive genomic profiling in clinical decision-making.

Reference: Gihawi, A., Wood, H. M., Clark, J., O’Grady, J., Eeles, R. A., Wedge, D. C., Jakobsdottir, G. M., Magiorkinis, G., Schache, A. G., Masterson, L., Lechner, M., Fenton, T. R., Jones, T. M., Flanagan, A. M., De Noon, S., Rubinsteyn, A., Hurst, R., Cooper, C. S., & Brewer, D. S. (2025). The landscape of microbial associations in human cancer. Science Translational Medicine. https://doi.org/10.1126/scitranslmed.ads6166

This work was funded by the Big C Cancer Charity and Prostate Cancer UK, with further support from The Bob Champion Cancer Trust, The Alan Boswell Group, Masonic Charitable Foundation Successor to the Grand Charity, Movember, Prostate Cancer Research, the King Family, the Hargrave Foundation, NIHR Manchester Biomedical Research Centre and Sarcoma UK.