Abstract A17: FBxW7 duality in ovarian cancer: Novel insight into ovarian cancer pathogenesis
Notice bibliographique
Résumé
Abstract Rationale: FBxW7 is a tumor suppressor gene that has been shown to be linked to ubiquitin-dependent proteolysis and regulation of the G1-S cell cycle checkpoint. FBxW7 mutations have been implicated in the impaired degradation of NOTCH, JUN, and cMYC, all of which have been demonstrated as key players in the ovarian cancer pathobiology. In this study we characterized the functional and prognostic significance of FBxW7 in ovarian cancer. Methods: Platinum-sensitive (A2780) and resistant (C200 and SKOV3) ovarian cancer cell lines were utilized, as well as cell lines derived from normal ovarian epithelium (IOSE). Ovarian cancer cell lines were transfected with FBxW7 constructs using Lipofectamine 2000tm. qPCR was performed to determine levels of gene and microRNA expression. Western blot analysis was performed to assess protein levels. Cell proliferation assays and FACS were performed determine cell proliferation and viability. A tissue microarray was used for immunohistochemical staining using FBxW7 antibody. Tissue stains were scored manually. Staining intensities were correlated with patient outcomes to calculate the overall survival and progression-free survival using Kaplan Meier methods and log-rank tests. Results: Upregulation of FBxW7 in platinum-sensitive cell lines decreases the substrates of FBxW7 ubiquitination, such as cMYC, NOTCH, and JUN. However, similar levels of FBxW7 expression did not decrease these substrate levels in platinum-resistant cell lines. microRNAs associated with stemness and chemoresistance also had differential expression profiles with FBxW7 transient transfection. Cell proliferation assays also highlighted differences between these sensitive and resistant cell lines. For tissue array analysis, 516 samples were used for FBxW7 IHC staining where 206 (40.2%) of samples were with high-grade serous histology. The majority of samples had FBxW7 staining of high intensity (273; 52.9%). There was no relationship between overall survival or progression-free survival and FBxW7 tissue staining in the total group. However, when analyzing only the high-grade serous histology, there was a trend of increased expression of FBxW7 being associated with better progression-free survival (p=0.051). Conclusions: Our studies suggest that FBxW7 have a dual role in ovarian cancer, having less effect on those cell lines associated with chemoresistance and stemness. In ovarian tumor tissues, there was a trend for elevated levels of FBxW7 expression and better progression free survival. Further studies on FBxW7 and its role in ovarian cancer pathogenesis are warranted. Citation Format: Elizabeth Louise Dickson, Lihua Li, Samuel Leung, Christine Chow, Rachel Isaksson Vogel, David Huntsman, C. Blake Gilks, Subbaya Subramanian. FBxW7 duality in ovarian cancer: Novel insight into ovarian cancer pathogenesis. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A17.
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 | 0,000 | 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 | 0,001 | 0,001 |
| 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 ».