Oncogenic role of SFRP2 in p53-mutant osteosarcoma development via autocrine and paracrine mechanism
Bibliographic record
Abstract
Significance Li–Fraumeni syndrome is a rare disorder caused by germline TP53 mutations, predisposing patients to early-onset cancers, including osteosarcoma (OS). Here we demonstrate that strong expression of SFRP2, a reported WNT antagonist, in OS patient samples correlates with poor survival and that SFRP2 overexpression suppresses normal osteoblast differentiation, promotes OS features, and facilitates angiogenesis via autocrine and paracrine mechanisms in an induced pluripotent stem cell disease model. We show that these SFRP2-mediated phenotypes are canonical WNT/β-catenin independent and are mediated through induction of oncogenes such as FOXM1 and CYR61. We further demonstrate that inhibition of SFRP2, FOXM1, or CYR61 represses tumorigenesis. Our data suggest that inhibition of SFRP2 should be explored clinically as a strategy for treatment patients with p53 mutation-associated OS.
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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 | 0.001 | 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".