Abstract P6-02-03: Leptin receptor (OB-R) in breast carcinoma tissue: Ubiquitous expression and correlation with leptin-mediated signaling, but not with systemic markers of obesity
Notice bibliographique
Résumé
Abstract Background/Aims: Obesity is associated with a 30-50% increased risk of breast-cancer (BC) mortality, most consistently in estrogen receptor (ER) positive disease, through unclear mechanisms. Leptin is a multi-functional protein with key actions on adipose tissue. In pre-clinical studies, leptin stimulates the growth, survival, and progression of BC cells through both estrogen dependent and other (e.g. JAK/STAT, PI3K/Akt, MAPK) pathways. Leptin has also been associated with increased BC risk and poor prognosis. Our aim was to correlate tumor leptin-receptor (OB-R) expression with tissue markers of cell signaling and systemic markers of obesity, inflammation, and metabolism in a cohort of ER+/HER2- BC patients. Methods: From our biorepository, we identified ER+/HER2- BC patients having both blood and tissue samples available. Data included BMI, menopausal status, and family/cancer/medical history, tumor histology, grade, stage, and ER/PgR/HER2 status. We performed blood assays for factors related to inflammation, tumor growth, hormonal regulation, and metabolism (see below). Immunohistochemistry for OB-R, pAkt (S473), pERK (T202/Y204), and insulin-receptor (IR) was performed on archived tissue, and scored for % positive cells and intensity of staining. Allred and H-scores were calculated. Associations with OB-R scores were calculated using Pearson, Spearman, and χ2 methods. Results: 129 patients were eligible; 69.8% were post-menopausal and mean BMI was 27.8 ± 6.5 kg/m2. Most tumors were no-special-type (79%), PgR+ (90%), and node-neg (78%). The tissue expression of OB-R and other markers was scorable in 118 (91%) cases. OB-R was expressed in all 118/118 cancers (Allred score range: 3 to 8; median 7, mean 6.61). High blood leptin did not downregulate OB-R (Spearman R=0), even though leptin was strongly correlated with BMI (Pearson r=0.78, p<0.00001). Increasing OB-R correlated with phosphorylation of Akt (R=0.19) but not ERK (R=0.08). By contrast, high BMI was associated with lower Akt (R=-0.18) and ERK (R=-0.11) phosphorylation. OB-R correlated with ER (Spearman R = 0.27), PgR (R=0.29), and insulin receptor (R = 0.24), weakly correlated with estradiol (Spearman, R=0.11) and fasting glucose (R=0.18), and negatively correlated with systemic IL-2 (R=-0.11) and IL-6 (R=-0.21). OB-R was not correlated with other blood markers (insulin, HOMA, PAI-1, IL-1ẞ, IL-8, VEGF, EGF, TNF-α,hsCRP, SHBG, or estrogens) or tumor grade. Conclusions: OB-R is highly expressed in breast tumor tissue even in non-obese patients. Although leptin and BMI did not modulate OB-R expression, downstream signaling (e.g. Akt, ERK) did show a BMI-dependent effect, albeit of limited magnitude. This suggests that leptin acts on breast cancer cells through OB-R activation and downstream Akt/ERK signaling, without a coupled change in total OB-R expression. Further work is needed to elucidate the roles of inflammation, estrogens, and regulatory mechanisms within the PI3K-PTEN and Ras-MAPK cell-signaling networks. The authors wish to acknowledge the generous support of the Breast Cancer Research Foundation and Hold'Em For Life Charity Challenge. Citation Format: Chang MC, Ennis M, Dowling RJO, Stambolic V, Goodwin PJ. Leptin receptor (OB-R) in breast carcinoma tissue: Ubiquitous expression and correlation with leptin-mediated signaling, but not with systemic markers of obesity [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-02-03.
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 | 0,001 |
| 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) | 0,005 | 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 ».