Urinary Eubacterium sp. CAG:581 promotes non-muscle-invasive bladder cancer (NMIBC) development through ECM1/MMP9 pathway
Bibliographic record
Abstract
Abstract Background: Increasing evidence points to the urinarymicrobiota as a possible key susceptibility factor for early-stage bladder cancer(BCa) progression. However, its underlying mechanism interpretation is often insufficient, given that various environmental conditions have affected the composition of urinary microbiota. Herein, we sought to rule out confounding factors and clarify how urinary Eubacterium sp. CAG:581 promoted non-muscle-invasive bladder cancer (NMIBC) development. Methods: Differentially abundant urinary microbiota of 51 NMIBC patients and 47 healthy controls as the Cohort 1 were firstly determined by metagenomics analysis. Then we modeled the coculture of NMIBC organoids with candidate urinary Eubacterium sp. CAG:581 in anaerobic condition and explored differentially expressed genes of NMIBC organoids by RNA-Seq. Furthermore, we dissected the mechanisms involved into Eubacterium sp. CAG:581-induced extracellular matrix protein 1 (ECM1) and matrix metalloproteinase 9 (MMP9) upregulation. Finally, we used multivariate Cox modeling to investigate the clinical relevance of urinary Eubacterium sp. CAG:581 16S ribosomal RNA (16SrRNA) levels with the prognosis of 406 NMIBC patients as the Cohort 2. Results: Eubacterium sp. CAG:581infection accelerated the proliferation of NMIBC organoids (P < 0.01); ECM1 and MMP9 were the most upregulated gene induced by increased colony forming units (CFU) gradient of Eubacterium sp. CAG:581 infection, via phosphorylating ERK1/2 in NMIBC organoids of the Cohort 1. Excluding the favorable impact of potential contributing factors, ROC curve of the Cohort 2 manifested its 3-year AUC value as 0.79 and the cut-off point of Eubacterium sp. CAG:581 16SrRNA as 10.3 (delta CT value). Conclusion: Our evidence suggests that urinary Eubacterium sp. CAG:581 promoted NMIBC progression through ECM1/MMP9 pathway, which may serve as the promising noninvasive diagnostic biomarker for NMIBC.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".