Abstract 5513: Role of the evolutionarily conserved TBX2 subfamily of transcription factors in the molecular pathogenesis of human lung adenocarcinoma
Notice bibliographique
Résumé
Abstract T-box (TBX) transcription factors are evolutionary conserved genes and master regulators of transcription repression and activation. In mammals, 18 members were described functionally and structurally, of which the TBX2 subfamily (TBX2, TBX3, TBX4, TBX5) genes were shown to be expressed early on in the developing lung bud and tracheae. Despite these insights into the role of the TBX2 subfamily in normal lung organogenesis, little is known about the role of these genes in pathological pulmonary conditions in humans; particularly lung cancer, an aggressive malignancy that is the leading cause of cancer-deaths worldwide. To fill this void, our group previously surveyed the expression of TBX2 subfamily in various publicly available datasets and found that all four members were preferentially and highly expressed in human normal lung, but markedly and consistently suppressed in lung adenocarcinoma (LUAD) the most common histological subtype of lung cancer. We also showed that the subfamily was also suppressed in preneoplastic lesions preceding the development of LUADs. Following the above and to further elucidate the role of the TBX2 subfamily in LUAD pathogenesis, we first probed and confirmed abundant expression of protein products of the four members by immunostaining in adult human normal lung tissues. On the other hand, quantitative real-time PCR and western blotting analyses demonstrated overall suppressed expression of the genes and corresponding proteins in a panel of human LUAD cell lines. Transient over-expression of each of the four genes in human LUAD cell lines (H1299 and H1944) was found to overall significantly inhibit cancer cell growth and proliferation. Additionally, over-expression of the four genes induced apoptosis, evidenced by sub-G0/G1 accumulation following cell cycle analysis, in both cell lines (ranging from 40% to 90% compared to control). To understand genome-wide effects of TBX2 subfamily in LUAD, we interrogated global expression programs downstream of these transcription factors by RNA-Seq in H1299 cells engineered to over-express the four members separately. We unraveled novel signaling cues signifying canonical pathways found in our analysis to be directly regulated by members of the TBX2 subfamily. These included, among others, inhibition of cell cycle progression and glycolysis, suppression of pathways mediated by epidermal growth factor (EGFR) and WNT signaling and activation of the major anti-tumor immune marker interferon gamma (IFNG). All in all, our findings point to tumor suppressor roles for TBX2 subfamily in human LUAD pathogenesis and suggest “oncophenotypes” downstream of these factors as putative targets for lung cancer therapy. Citation Format: Athar Khalil, Nehme El-Hachem, Batoul Dekmak, Humam Kadara, Georges Nemer. Role of the evolutionarily conserved TBX2 subfamily of transcription factors in the molecular pathogenesis of human lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5513.
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) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| 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) | 0,004 | 0,002 |
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 ».