Abstract 5038: The repression of the extracellular matrix protein TGFBI induces chemoresistance in nasopharyngeal carcinoma
Notice bibliographique
Résumé
Abstract Introduction: Nasopharyngeal carcinoma (NPC) is a malignancy that is strongly associated with Epstein-Barr virus (EBV). The five-year overall survival (OS) rate of locally-advanced NPC patients is ∼65%. Therapeutic options for such patients are limited; ionizing radiation is the primary mode of therapy for early-stage NPC, while chemoradiotherapy is used for more advanced stages. The use of chemotherapy (combined with radiation) provides a modest benefit in OS, but causes significant toxicities. The major cause of death in NPC is distant metastasis (DM), which remains a clinical challenge. In order to identify novel mechanisms underlying this process, our laboratory has recently completed global RNA sequencing of NPC samples which were fully clinically annotated. The extracellular matrix protein TGFBI (Transforming Growth Factor, Beta-Induced) was identified as a potential marker for chemoresistance. The objective of this study was to elucidate the role of TGFBI, and acquire greater insight into the biological pathways leading to chemoresistance and contributing to DM in NPC. Methods: Nasopharyngeal cell lines including NP69 (normal nasopharyngeal, SV-40 immortalized), and C666-1 (NPC, EBV positive) were used to assess the differential expression of TGFBI between normal and malignant cells. TGFBI under-expressing NP69 cells were engineered using shRNA vectors, and the impact of the loss of TGFBI expression was assessed by cell death, clonogenic, and migration assays. Downstream target gene expression was evaluated by quantitative real-time PCR (qRT-PCR) and Western blot. C666-1 cells, which had no expression of TGFBI (RNA or protein), were used as controls. Results: RNA-seq data identified poorer distant relapse-free survival in chemoradiotherapy-treated patients with low TGFBI expression vs. those with high TGFBI expression. In concordance with this observation, in vitro down-regulation of TGFBI induced cisplatin resistance via the phosphorylation of Akt and PTEN. TGFBI downregulation also increased cellular migration in spheroid cultures. Furthermore, TGFBI was identified to be a target of miR-449b, one of the 4 microRNAs in a DM prognostic signature that was previously identified by our group (Oncotarget 6:4537, 2015). In turn, over-expression of miR-449b in nasopharyngeal cells increased phospho-Akt expression, phenocopying the results observed in the TGFBI experiments. Conclusion: Together, these data suggest that the miR-449∼TGFBI-Akt axis plays a significant role in both treatment resistance and metastasis in NPC. Further studies will allow us to elucidate additional components of this pathway, and identify novel therapeutic targets which can benefit future patients with NPC. Citation Format: Pierre-Antoine Bissey, Jeff W. Bruce, Jacqueline Law, Kenneth W. Yip, Fei-Fei Liu. The repression of the extracellular matrix protein TGFBI induces chemoresistance in nasopharyngeal carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5038.
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 | 0,000 | 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 ».