Abstract 3038: Characterization of ZHX1 in node-negative breast cancer
Notice bibliographique
Résumé
Abstract Women with breast cancer but without local metastasis to the axillary lymph nodes (ANN) have a good prognosis. However, 20 to 30% of patients with ANN breast cancer will still experience recurrence and distant metastases. Lymphatic invasion (LVI) is an important prognostic factor for ANN breast cancer. Therefore, LVI status was incorporated to provide a unique approach to identify novel genes related to outcome in ANN breast cancer. Gene expression microarrays were used to discriminate between tumors 1) with or without LVI (LVI+ or LVI-, respectively) and 2) from patients who experienced early recurrence (within 4 years) and those who were disease-free (for at least 10 years). Biostatistical analyses were performed to compile a list of statistically significant genes common to both comparisons. Zinc fingers and homeoboxes 1 (ZHX1) was identified as a candidate gene involved in LVI and associated with early recurrence of ANN breast cancer. Real-time RT-PCR (qPCR) was performed to quantify ZHX1 expression in a subset of cell lines and tumor samples. ZHX1 is expressed at different levels, mostly at an intermediate level in the tumors. A more network-based approach was used to examine biological pathways that may be associated with this poor prognosis. We discovered that ZHX1 may be involved in transcription, signaling, metabolism, and development, which is consistent with previous findings. ZHX1 binds to the other two members of the ZHX family, ZHX2 and ZHX3. All three members bind to the activation domain of the alpha subunit of nuclear transcription factor γ (NF-γ). NF-γ activates transcription of several genes, including the cell cycle progression gene, cell division cycle 25 homolog C (CDC25C). However, ZHX2 represses promoter activity of CDC25C, which would prevent cells from progressing into mitosis. Since ZHX1 binds to ZHX2 and NF-γ, this suggests that ZHX1 may be involved in the cell cycle. ZHX1 is significantly over-expressed in LVI+ tumors and in those from patients who experienced early recurrence of ANN breast cancer. The potential role of ZHX1 in the cell cycle may be associated with this poor prognosis. Gene and protein expression of ZHX1 and its candidate interactors are being quantified in cell lines via qPCR and Western blotting, respectively, and potential correlations examined. Immunohistochemistry is being performed on tissue microarrays to observe ZHX1 protein levels and localization and correlate with gene expression. Cell lines are being transfected via vector- or siRNA- based methods to over-express or knock down ZHX1, respectively. Alterations in tumorigenicity are being investigated via MTT proliferation and migration and/or invasion assays. Findings may aid in determining which ANN breast cancer patients may benefit from systemic therapy and identifying novel targets for cancer therapeutics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3038. doi:10.1158/1538-7445.AM2011-3038
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) | 0,001 | 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 ».