Rounbehler, R. J. | Search bioRxiv

bioRxiv2025

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.

cancer biology↗

bioRxiv2019

Commercial gene expression tests for prostate cancer prognosis provide paradoxical estimates of race-specific risk

BackgroundCommercial gene expression signatures of prostate cancer (PCa) prognosis were developed and validated in cohorts of predominantly European American men (EAM). Limited research exists on the value of such signatures in African American men (AAM), who have poor PCa outcomes. We explored differences in gene expression between EAM and AAM for three commercially available panels recommended by the National Comprehensive Cancer Network for PCa prognosis. Materials and Methods: 232 EAM and 95 AAM patients provided radical prostatectomy specimens. Gene expression was quantified using Nanostring for 60 genes spanning the Oncotype DX Prostate, Prolaris, and Decipher panels. A continuous expression-based risk score was approximated for each. Differential expression, intrapanel co-expression and risk by race were assessed.\n\nResults and limitationsClinical and pathologic features were similar between AAM and EAM. Differential expression by race was observed for 48% of genes measured, though the magnitudes of expression differences were small. Coexpression patterns were more strongly preserved by race group for Oncotype DX and Decipher versus Prolaris (integrative correlations of 0.87, 0.73, and 0.62, respectively). Poorer prognosis was estimated in EAM versus AAM for Oncotype DX (p < 0.001), whereas no difference in prognosis was predicted between AAM and EAM using Prolaris or Decipher (p > 0.05). Replication of our findings directly on the commercial panels with long-term follow-up is warranted.\n\nConclusionsDue to observed racial differences across three commercial gene expression panels for PCa prognosis, caution is warranted when applying these panels in clinical decision-making in AAM.

epidemiology↗