Non-coding RNAs predict recurrence-free survival of patients with hypoxic tumours
Bibliographic record
Abstract
Hypoxia promotes tumour aggressiveness and reduces patient survival. A spectrum of poor outcome among patients with hypoxic tumours suggests that additional factors modulate how tumours respond to hypoxia. PIWI-interacting RNAs (piRNAs) are small non-coding RNAs with a pivotal role in genomic stability and epigenetic regulation of gene expression. We reported that cancer type-specific piRNA signatures vary among patients. However, remarkably homogenous piRNA profiles are detected across patients with renal cell carcinoma, a cancer characterized by constitutive upregulation of hypoxia-related signaling induced by common mutation or loss of von Hippel-Lindau factor (VHL). By investigating >3000 piRNA transcriptomes in hypoxic and non-hypoxic tumors from seven organs, we discovered 40 hypoxia-regulated piRNAs and validated this in cells cultured under hypoxia. Moreover, a subset of these hypoxia-regulated piRNAs are regulated by VHL/HIF signaling in vitro. A hypoxia-regulated piRNA-based score (PiSco) was associated with poor RFS for hypoxic tumours, particularly Stage I lung adenocarcinomas, suggesting that hypoxia-regulated piRNA expression can predict tumour recurrence even in early-stage tumours and thus may be of clinical utility.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".