Abstract 3161: Identification of HPV/p16-associated microRNAs in primary oropharyngeal carcinoma
Notice bibliographique
Résumé
Abstract Introduction: Deregulation of micro-RNAs (miR) is associated with oncogenesis of various malignancies, suggesting that miR expression profiling have the potential to unravel the complex biology of human tumours. It is now established that human papillomavirus (HPV)-associated oropharyngeal carcinoma (OPC) is a completely distinct entity, with a significantly more favourable outcome, compared to HPV-negative OPCs. The mechanisms underlying these differences currently remain incompletely understood; we therefore postulated that miR profilings might offer additional biological insights. Hence, the objectives of this study were to determine whether: a) there were miRs which associate with HPV (or p16) status; and b) there might be any association with clinical outcome, independent of HPV (or p16) status. Experimental Procedures: Archival formalin fixed and paraffin embedded (FFPE) diagnostic biopsy specimens were collected from 88 non-metastatic OPC samples (p16+ve:58; p16-ve:34), from patients who were treated for cure, as per institutional guidelines. Macrodissection was performed to ensure that each specimen contained >70% tumor cells. Seven FFPE specimens derived from histologically normal tonsils were used as controls. RNA was isolated using a commercially available extraction kit designed specifically for FFPE samples (Ambion). Expression levels of 365 miRs plus 3 endogenous controls were simultaneously measured by quantitative RT-PCR using the Human TaqMan Low Density Array (Applied Biosystem). Results: Four patient samples were excluded due to poor RNA quality. Overall, 224 miRs were expressed in >80% of both tumors and normal samples. Slightly more than half (128/224; 57%) of miRs were significantly differentially expressed between tumor and normal tissues (p<0.05); the majority of which (120/128; 94%) were up-regulated in tumor samples. The top 5 most significantly up-regulated miRs were miR-21, let-7g, miR-25, let-7f and miR-130b. It was noted that many of the deregulated miRs were located at known fragile sites of the chromosome. The top 5 most significantly p16-associated miRs included up-regulated miR-20b, miR-9, miR-9*, as well as down-regulated miR-193b and miR-23a. Further analyses identified three potential miR sets that associated with overall survival (miR-107, miR-151, miR-492; p=0.0002), disease free survival (miR-107, miR-151, miR-182, miR-20b, miR-361; p=0.0001), and distant metastasis (miR-324-5p, miR-151, miR-152, miR-361, miR492; p=0.0087), which retained significance even after adjusting for p16 status. Conclusions: We have identified a panel of p16/HPV-associated miRs in OPC, which appear to associate with clinical outcome, independent of p16 status. These data require further validation, but further evaluations of these miRs might offer biological insights into the mechanisms underlying the differences between HPV-positive vs. HPV-negative OPC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3161. doi:1538-7445.AM2012-3161
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 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 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) | 0,003 | 0,001 |
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 ».