Abstract 883: Genetic characteristics between males and females with urothelial bladder cancer
Notice bibliographique
Résumé
Abstract Urothelial bladder cancer (UBC) affects the epithelial cells of the urinary tract and is the most common type of bladder cancer worldwide. Statistically, males are four times more likely to develop UBC than females. It is known that decreased expression of the KDM6A gene, coded on the X chromosome, corresponds with a higher incidence of UBC. KDM6A mutations are known to be more prevalent in females with non-muscle-invasive UBC. These mutations are targetable by inhibiting EZH2, an enzyme coded by its namesake gene. On the environmental side, males are at a higher risk of developing carcinogenic complications due to smoking and environmental toxins. However, this discrepancy fails to exist when comparing males and females who smoke similar levels. Though environmental factors may play a role in influencing behavior and altering levels of risk to develop UBC, research suggests that they do not single-handedly explain sex-based disparities in UBC. In this study, we characterize the molecular mechanisms associated with altered overall survival by uncovering previously unreported data on the expression of KDM6A and FGFR3, a commonly altered oncogene, in UBC patients. Our in silico approach consisted of broad survival data analysis through cBioPortal (n=1486), sequencing-based gene expression data through ICGC Portal (n=295), and single nucleotide polymorphism identification with the PLCO Atlas (n=69,429). The 5-year overall survival (OS) curves of 13 therapeutic and/or significantly altered genes between males and females were analyzed. BRCA2 was the only gene associated with worse survival for females with alterations. Interestingly, males with alterations to the following genes had significantly better OS outcomes: ERCC2, KDM6A, BRCA2, FGFR3. However, there was no gene whose alterations were associated with significantly better OS outcomes for females. KDM6A and FGFR3, two genes whose alterations are typically associated with worse OS outcomes in males, exhibit the opposite effect. Additionally, males exhibited significantly worse OS outcomes when presenting with CDKN2A and CDKN2B alterations, while females exhibited significantly worse OS outcomes when presenting with CDKN2A and NTRK1. A majority of European males had SNPs on the following genes: CDKN2B, ERBB2, CREBBP, while a majority of European females had SNPs on BRCA2. Differential expression also revealed 714 genes that were significantly expressed in one sex when compared to the other. Therefore, we suggest that there are unique molecular differences between sex that conflict with previous analyses; further research should be conducted to explore the effect of sex via the tumor-suppressive characteristics of KDM6A as well as oncogenic properties of FGFR3. Citation Format: Rishi Nair, Roy Khalife, Anthony Magliocco. Genetic characteristics between males and females with urothelial bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 883.
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) | 0,006 | 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 ».