Primary tumor microbiomes predict distant metastasis of colorectal cancer
Metastasis causes most cancer-related deaths in colorectal carcinoma (CRC), and microbiome markers may have prognostic value. We hypothesized that primary tumor microbiomes predict distant metastases. We analyzed 5-year metastasis-free survival (MFS) in a retrospective cohort of 900 ORIEN CRC tumor microbiomes (RNAseq). ORIEN findings were validated on an independent cohort using 16S rDNA sequencing and pathobiont-specific qPCR. Microbiome alpha diversity was higher in primary tumors than metastases and positively correlated with metastasis risk. Microbiome beta diversity distinguished primary vs. metastasis and predicted 5-year MFS. High primary tumor abundance of B. fragilis and low F. nucleatum were associated with short MFS. Enterobacteriaceae, including E. coli, were enriched in metastases. qPCR identified increased enterotoxigenic B. fragilis and pks + E. coli detection in CRC metastasizers. Microbial co-occurrence analysis identified a 3-species clique that predicts metastasis (OR 1.9 [1.4-2.6]). Results suggest that primary tumor microbiomes and specific pathobionts are precision markers for metastasis risk.
Authors
- Thèrése Bocklage (ORCID: https://orcid.org/0000-0003-0899-9405)
- Ashiq Masood (ORCID: https://orcid.org/0000-0002-1848-1178)
- Gregory Riedlinger (ORCID: https://orcid.org/0000-0001-5690-7777)
- Vishal Midya (ORCID: https://orcid.org/0000-0002-6643-5176)
- Craig D. Shriver (ORCID: https://orcid.org/0000-0001-8993-5811)
- Nadia de Jager
- Robert J. Rounbehler
- Ahmad A. Tarhini (ORCID: https://orcid.org/0000-0002-3193-9702)
- Rebecca Hoyd (ORCID: https://orcid.org/0000-0003-1210-4491)
- Bodour Salhia
- Song Yao (ORCID: https://orcid.org/0000-0001-9442-1313)
- Daniel Spakowicz (ORCID: https://orcid.org/0000-0003-2314-6435)
- Dinesh Pal Mudaranthakam (ORCID: https://orcid.org/0000-0001-9767-1158)
- Sheetal Hardikar (ORCID: https://orcid.org/0000-0003-0292-6168)
- Melanie R. Rutkowski (ORCID: https://orcid.org/0000-0001-8604-815X)
- Robert W. Lentz (ORCID: https://orcid.org/0000-0002-7207-8195)
- Carlos H.F. Chan (ORCID: https://orcid.org/0000-0003-3656-2470)
- Michelle L. Churchman (ORCID: https://orcid.org/0000-0002-6560-1056)
- Hassan Hatoum (ORCID: https://orcid.org/0000-0001-7553-1963)
- Mmadili N. Ilozumba (ORCID: https://orcid.org/0000-0002-9928-3711)
- June L. Round (ORCID: https://orcid.org/0000-0002-7158-9874)
- Shoshannah Eggers (ORCID: https://orcid.org/0000-0002-4321-9219)
- Dustin E. Bosch (ORCID: https://orcid.org/0000-0002-7430-2939)
- Cornelia M. Ulrich
- Bashu Dev Parajuli
- Ryan Kiddle
Institutions
- Rutgers, The State University of New Jersey (US)
- University of Southern California (US)
- University of Iowa (US)
- Indiana University Health (US)
- Roswell Park Comprehensive Cancer Center (US)
- University of Kentucky (US)
- University of Dubuque (US)
- Uniformed Services University of the Health Sciences (US)
- University of Utah (US)
- Huntsman Cancer Institute (US)
- Moffitt Cancer Center (US)
- The University of Kansas Cancer Center (US)
- Indiana University School of Medicine
- University of Oklahoma Health Sciences Center (US)
- University of Virginia (US)
- The Ohio State University (US)
- Indiana University – Purdue University Indianapolis (US)
- University of Colorado Denver (US)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- npj Precision Oncology
- Published
- 2025-11-24
- DOI
- https://doi.org/10.1038/s41698-025-01188-x
- Citations
- 1
- Primary Topic
- Cancer Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 1.23
Funders
- National Institutes of Health
- Holden Comprehensive Cancer Center, University of Iowa
- National Cancer Institute