Abstract 2404: Change in expression of microRNAs following limb amputation in canine osteosarcoma patients predicts survival time after chemotherapy
Notice bibliographique
Résumé
Abstract Osteosarcoma (OS) is the most common primary bone tumour in dogs and humans. There are an estimated 8, 000 new cases of canine OS per year in the United States compared to only 1, 000 in humans. The most common primary location for both species is the appendicular skeleton, with metastases forming mostly in the lungs and bones. Appendicular OS is not only more common in dogs, but also more aggressive, making dogs a valuable spontaneously metastasizing animal model of aggressive human OS. Median survival after amputation and adjuvant chemotherapy in dogs is 1 year, less than 30% survive 2 years, and an estimated 90% of dogs develop metastases after therapy. In contrast, humans have a 76% 5-year survival rate and 15-25% will develop metastases. Predicting clinical outcomes after treatment is difficult in both species, particularly for those without clinically detectable metastatic disease at diagnosis. MicroRNAs (miRNAs) are small, non-coding RNA that control gene expression and are often dysregulated in cancer. MiRNAs share entirely or nearly identical sequences between dogs and humans and are present in blood, making them good potential biomarkers. Recently, we identified multi-miRNA models which could reliably predict survival using pre-amputation canine OS plasma samples. Tumour cells can release miRNAs into the blood via active and passive mechanisms; therefore, with the primary tumour removed after amputation, miRNA expression levels in the blood should be altered. We hypothesize these changes in miRNA expression can be used to prognosticate canine OS patients better. MiRNA expression was measured using real-time quantitative PCR in matched pre- and post-amputation plasma samples from canine OS patients (n=25) at the Ontario Veterinary College. Change in expression was calculated for each miRNA as [(post-amputation) - (pre-amputation)] for each matched pair of samples. For each dog, survival was measured as overall survival and disease-free interval (DFI). Overall survival is the time from diagnosis to death and DFI is the time from diagnosis to clinically detectable metastasis. Dogs were censored if they died from non-OS events, were lost during follow-up, or were still alive. Prognostic ability was evaluated for individual miRNAs by identifying an optimal expression cutoff point using the survminer package in R and visualized using Kaplan-Meier curves. Decision trees were grown using the rpart package in R to evaluate whether multi-miRNA models offered improved prognostic ability compared to single miRNAs. We found that a model combining miRNA-144 and miRNA-23a, for both overall survival and DFI metrics, was able to identify 3 distinct groups which reflected survival time worse, on par, and better than the median survival time reported in literature. These models offer a simple prognostic test that may have clinical applications for veterinary and human OS patients. Citation Format: Heather Treleaven, Michael Edson, Latasha Ludwig, Alicia Viloria-Petit, R. Darren Wood, R. Ayesha Ali, Geoffrey A. Wood. Change in expression of microRNAs following limb amputation in canine osteosarcoma patients predicts survival time after chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2404.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».