Abstract P4-09-07: ING1 Expression Measured by AQUA can be an Independent Prognostic Marker in Breast Cancer
Notice bibliographique
Résumé
Abstract Background: Breast cancer accounts for around 45,000 cancer related deaths in North America per year. The high incidence of breast cancer observed in this region is most likely due to the availability of various screening programs used to detect breast cancer, which otherwise may never get diagnosed. There is an inverse relation between the cost of treatment and patient survival as the breast cancer progresses to higher grades. Therefore, screening and diagnosing breast cancers at earlier stages is needed which can improve patient survival. The INhibitor of Growth (ING) family of tumour suppressor proteins are implicated in diverse cellular processes including chromatin remodelling and apoptosis. ING proteins are stoichiometric members of histone acetyl transferase (HAT) and histone deacetylase (HDAC) complexes. Their expression is downregulated in several cancers, including breast carcinoma. Alternatively, ING function may be compromised by mislocalization to the cytoplasm. However, the association of expression of ING proteins and cancer specific survival has not been studied yet. In this study, we aimed to evaluate the prognostic significance of ING1 in breast cancer. Patients and Methods: This study included 443 Breast Cancer patients diagnosed in Calgary, Canada from 1985–2000. Clinical data were obtained from the Alberta Cancer Registry and chart review. Tissue microarrays (TMAs) were assembled from triplicate cores of formalin-fixed paraffin-embedded tumour tissue. ING1 protein expression was quantified using fluorescent immunohistochemistry and automated quantitative analysis (AQUA) in normal breast epithelial cells and breast cancer samples. 5 year progression free survival (PFS) was analyzed using Kaplan-Meier plots and Cox proportional hazard modelling. Results: In our study, we found that ING1 expression is significantly downregulated in the breast cancer patient samples relative to normal breast epithelia. High or low ING1 cytoplasmic/nuclear (C/N) ratio results in poor 5 year PFS. Also, the low tumor/stromal (t/s) ratio of ING1 results in poor prognosis. In univariate analysis, t/s ING1 expression showed a negative correlation with tumor stage [p = 0.008]; tumor grade [p = 0.000]; nodal status [p = 0.000] and 5 year PFS [p = 0.004]. However, no correlation was observed with ER, PR or HER2 status. In multivariate analysis, t/s ING1 proved to be an independent and better prognostic marker [HR 0.582, p = 0.037] than HER2 [HR 2.230, p = 0.057]; Age at diagnosis [HR 2.010, p = 0.205] and tumor size [HR 1.471, p = 0.189]. Discussion and Conclusions: This is the first study to evaluate ING1 expression in breast cancer using the AQUA technique. ING1 expression high or low in the C/N ratio might disrupt the stoichiometry of chromatin-modifying complexes and hamper ING1s extra nuclear functions, leading to poor survival. The significantly improved survival observed in patients with high t/s ING1 expression further strengthens the role of ING1 as a tumor suppressor. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-09-07.
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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) | 0,004 | 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 ».