Abstract 3114: Soy isoflavones modulate global methylation in head and neck squamous cell carcinoma (HNSCC)
Notice bibliographique
Résumé
Abstract Soy intake has been associated with improved survival in HNSCC and soy isoflavones have been suggested as potential chemopreventive agents with a favorable therapeutic index and safety profile. Multiple in vivo and in vitro anti-cancer effects have been postulated including modulation of gene methylation. To determine if high dose soy isoflavone treatment changes methylation of genes associated with cancer outcomes, we measured genomic and gene-specific methylation in tumor tissue collected as a part of a multi-institutional neoadjuvant soy isoflavone clinical trial in HNSCC patients undergoing definitive surgical management. Methods: Thirty-nine patients participated in this clinical trial. Patients were scheduled to receive 2 weeks (range 7-39 days, median = 15.2) of soy isoflavone supplements (300 mg/day G-2535; DCP, NCI, NIH) orally prior to surgery. Levels of methylation of LINE-1 (global methylation), and 6 other candidate genes previously associated with HNSCC (p16, DCC, NDN, CD1a, CCNA1 and Gadd45α) were measured by pyrosequencing in biopsy, resection and whole blood specimens. Twelve patients were stage I/II, 27 were stage III/IV. Thirty one patients had cancer of the oral cavity, 4 had larynx and 4 had oropharynx cancer. Mean age of the patients was 60.1 (sd = 12.5). Changes in methylation were tested using paired t-tests and clinical associations explored using ANOVA. Results: LINE-1 methylation increased significantly (mean increase 4.9%; range -34.8% to +20.9%) in tumor specimens after soy isoflavone (p<0.005). Amount of change correlated positively with days of isoflavone taken (p = .009). Increases in LINE-1 methylation in tumor were greatest in patients with normal BMI (p<0.03). Similar changes for LINE-1 were not seen in corresponding whole blood samples. No other significant changes in tumor or blood methylation levels were seen in the other candidate genes. Baseline tumor methylation and change in methylation were also studied with respect to nutrition (BMI), drinking, tumor site, tumor stage, nodal status and prior treatment. Baseline CD1a methylation was lowest in current smokers (p<0.04) and increases in CD1a after soy intake were associated with increasing pack years (p<0.02). CD1a methylation was also higher in patients with T1,2 tumors (p<0.03). Pretreatment NDN methylation was lower (p<.008) and LINE-1 higher (p<0.0001) in oral cavity cancer compared to oropharynx or larynx cancers. Toxicity from soy isoflavones was negligible and patient compliance was excellent. Conclusions: This is the first demonstration of significant increases in tissue-specific global methylation associated with soy isoflavone intake, indicating increased genomic stability. The association of hypomethylation of LINE-1 with genetic instability, carcinogenesis and poor treatment outcomes suggests that soy isoflavones should be studied further as a potential chemopreventive agent in HNSCC. Citation Format: Laura Rozek, Shama Virani, Emily Bellile, Jeremy Taylor, Maureen Sartor, Alisha Virani, Katie Rentschler, Claire Cote, Francis Worden, Lisa Peterson, Douglas Chepeha, Mark Prince, Scott McLean, George Yoo, Neil F. Saba, Dong M. Shin, Omer Kucuk, Gregory T. Wolf. Soy isoflavones modulate global methylation in head and neck squamous cell carcinoma (HNSCC). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3114.
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) | 0,002 | 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 ».