Abstract P4-09-08: miR-135a is associated with a metastatic phenotype in invasive lobular carcinoma
Notice bibliographique
Résumé
Abstract Invasive lobular carcinoma (ILC) is the second most common type of breast cancer. Classic type ILC is generally regarded as indolent in nature with its favourable biologic characteristics such as low grade, ER positivity and luminal A subtype. Despite this, patients with ILC can develop significant distant recurrence or metastases. Thus the ability to identify those patients at highest risk of recurrence or metastasis, and identification of novel therapies for ILC are urgently required. To this end, we recently profiled the miRNA expression in primary surgical ILC specimens from patients who went on to have metastatic disease compared to those who remained tumor free long term. As miRNA are stable in formalin fixed paraffin embedded tissues1, we speculated they could be robust biomarkers. RNA was isolated from laser capture microdissected ILC tumor epithelium, and subjected to miRNome analysis using a PCR-based amplification method. Many differentially expressed miRNAs were identified, and we initially focused further validation on those which had been previously linked to metastasis. One of these, miR-135a, was elevated in tumors from ILC patients who developed metastases compared to those that did not. We utilized two representative ILC cell lines which differ in their invasive ability, MDA-MB-134VI (non-invasive) and MDA-MB-330 (invasive), to test whether miR-135a regulated ILC invasion. We found that levels of miR-135a correlated with the invasive potential of ILC cell lines and was elevated in the invasive MDA-MB-330 cells compared to less invasive MDA-MB-134VI cells. We also found that decreasing miR-135a expression using specific hairpin inhibitors in MDA-MB-330 cells resulted in decreased cell invasion. As miR-135a has been shown to regulate invasion via targeting metastasis suppressor 1 (MTSS1) mRNA for degradation2, we examined whether MTSS1 levels were inversely associated with miR-135a levels in ILC cells. As predicted, in MDA-MB-330 cells where miR-135a levels were significantly higher, levels of MTSS1 were the lowest while MTSS1 levels were higher in parallel with decreased levels of miR-135a in the non-invasive MDA-MB-134VI cells. Overexpressing miR-135a using miRNA mimics in normal mammary epithelial cells (HMEC) where miR-135a is normally low, reduced levels of MTSS1 supporting suggestions it is a direct target of miR-135a. We also confirmed reduced mRNA levels of MTSS1 in surgical specimens from ILC patients who developed metastases compared to those that did not. Taken together, our results suggest that high levels of miR-135a, and low levels of MTSS1 may be useful prognostic information to assess risk of metastasis in ILC. References 1. Bovell L, Shanmugam C, Katkoori VR, et al: miRNAs are stable in colorectal cancer archival tissue blocks. Front Biosci (Elite Ed) 4:1937-40, 2012 2. Zhou W, Li X, Liu F, et al: MiR-135a promotes growth and invasion of colorectal cancer via metastasis suppressor 1 in vitro. Acta Biochim Biophys Sin (Shanghai) 44:838-46, 2012. Citation Format: Howe GA, Zhao H, Daneshmand M, Clemons M, Robertson SJ, Arnaout A, Addison CL. miR-135a is associated with a metastatic phenotype in invasive lobular carcinoma. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-09-08.
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 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 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) | 0,002 | 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 ».