Bacterial extracellular vesicles and microbial-derived small RNAs as circulating cancer biomarkers

Emerging evidence suggests that bacterial extracellular vesicles (BEVs) and microbial-derived small RNAs (msRNAs) in human plasma represent a new class of circulating cancer biomarkers. Multi-cohort analyses of more than 1100 patients revealed 2.8- to 3.5-fold higher BEV levels in cancer cases versus controls, with microbial RNA cargo comprising up to 1.6% of total plasma RNA. Specific BEV-msRNA panels achieved area under the curve values of 0.87-0.94 for early-stage cancer detection, outperforming conventional CEA and CA19-9 markers. Functionally, BEV-associated msRNAs modulate tumor-related signaling by activating NF-κB and STAT3 pathways and suppressing TP53/PTEN expression, promoting cytokine release and oncogenic inflammation. BEVs also exhibit superior stability remaining detectable for more than 72 hours in circulation supporting their feasibility for clinical liquid biopsy. Collectively, circulating BEVs and msRNAs offer promising, mechanism-linked biomarkers for non-invasive cancer detection and precision monitoring.