MP68-10 HOXB13 EXPRESSION AND ITS ROLE IN PROSTATE CANCER PROGRESSION AND NEUROENDOCRINE DIFFERENTIATION
Notice bibliographique
Résumé
You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology II (MP68)1 Apr 2019MP68-10 HOXB13 EXPRESSION AND ITS ROLE IN PROSTATE CANCER PROGRESSION AND NEUROENDOCRINE DIFFERENTIATION Farzana Faisal*, Mohammed Alshalalfa, Elai Davicioni, R. Jeffrey Karnes, William Isaacs, Tamara Lotan, and Edward Schaeffer Farzana Faisal*Farzana Faisal* , Mohammed AlshalalfaMohammed Alshalalfa , Elai DavicioniElai Davicioni , R. Jeffrey KarnesR. Jeffrey Karnes , William IsaacsWilliam Isaacs , Tamara LotanTamara Lotan , and Edward SchaefferEdward Schaeffer View All Author Informationhttps://doi.org/10.1097/01.JU.0000557025.09954.39AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVES: HOXB13 expression is involved in normal prostate development, is a known regulator of androgen receptor (AR)-mediated transcriptomes in prostatic tissue, and is also maintained in the formation of prostatic adenocarcinoma (PCa). In breast and other hormone-sensitive gynecological cancers, deregulated expression of HOXB13 correlates with aggressive tumor phenotypes and poor response to hormonal therapies. The predictive role of HOXB13 expression within prostate tumor progression and its associated outcomes remains unexplored. METHODS: We utilized HOXB13 RNA transcriptome expression from several datasets of PCa radical prostatectomy (RP) genome-wide expression profiles from the Decipher GRID registry and public cohorts (n=6,679). We compared levels of HOXB13 expression by tumor progression and by histology (adenocarcinoma, neuroendocrine/small cell). We assessed the association of HOXB13 expression with pathologic/oncologic outcomes and risk of metastasis based on genomic signatures (Decipher score). Finally, we analyzed gene expression profiling of canonical AR and AR-V7 targets to investigate the association of HOXB13 with AR signaling. RESULTS: There was a stepwise increase in the expression of HOXB13 from benign tissue, to primary tumor, to metastatic PCa (p=0.01). Increased levels of HOXB13 expression were associated with higher pathologic grade group (p<0.001), metastasis (p=0.001), and higher Decipher scores (p<0.001). In two retrospective cohorts (Hopkins, Mayo), higher HOXB13 expression was associated with decreased metastasis-free survival (p=0.02 and p=0.003, respectively). HOXB13 expression was also highly correlated to AR/AR-V7 target genes, NKX3-1 (r=0.73), and FOXA1 (r=0.67). Lower HOXB13 was associated with neuroendocrine biomarkers NCAM1 and ASXL3. Furthermore, HOXB13 expression was decreased in metastatic castrate-resistant PCa and neuroendocrine and small cell prostatic carcinoma (p<0.001). CONCLUSIONS: In primary PCa, HOXB13 expression increases with progression and is associated with higher AR signaling and adverse pathologic and oncologic outcomes. Though, its expression is lowered when PCa becomes castrate-resistant and when these cancers develop neuroendocrine differentiation. These data support the hypothesis that increased levels of HOXB13 confer a more aggressive PCa phenotype with metastatic potential. Future research can explore the role of HOXB13 not only as a biomarker of aggressive disease but also as a therapeutic target in PCa. Source of Funding: None Baltimore, MD; Vancouver, Canada; Rochester, MN; Baltimore, MD; Chicago, IL© 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 201Issue Supplement 4April 2019Page: e979-e979 Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.MetricsAuthor Information Farzana Faisal* More articles by this author Mohammed Alshalalfa More articles by this author Elai Davicioni More articles by this author R. Jeffrey Karnes More articles by this author William Isaacs More articles by this author Tamara Lotan More articles by this author Edward Schaeffer More articles by this author Expand All Advertisement PDF downloadLoading ...
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 | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,040 | 0,006 |
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 ».