GATA6 expression in advanced pancreatic ductal adenocarcinoma (PDAC) as a prognostic and predictive biomarker in the Canadian COMPASS trial and the Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS.
Notice bibliographique
Résumé
4150 Background: Modified FOLFIRINOX (mFFX) and gemcitabine + nab-paclitaxel (GnP) are current 1st line options in advanced PDAC. GATA6 expression, a transcription factor identifies the classical phenotype and is associated with superior overall survival (OS), low GATA6 predicts a basal-like phenotype, associated with a poorer prognosis. We have previously established high concordance between GATA6 expression by RNAseq and in situ hybridization (ISH). Recent studies suggest a survival difference between primary tumor anatomical locations, it is unknown if GATA6 expression influences this. This multicentre study evaluates GATA6 as a prognostic and predictive biomarker and determines its impact on primary tumor location. Methods: Patients were included from COMPASS and a retrospective IRCCS cohort. COMPASS participants had GATA6 by RNAseq and IRCCS cohort by ISH, all treated in 1st line metastatic setting with mFFX or GnP. The primary endpoint was OS by GATA6 expression and by 1st line treatment. We investigate if there are OS differences between primary tumor anatomical locations. The Kaplan Meier method was used to assess OS. The log-rank test was used to examine whether there is a significant difference between the OS in different groups. GATA6 as a predictive biomarker to response to therapy was assessed by the interaction term for GATA6 and treatment group in a Cox proportional hazards model. Results: The combined analysis included 465 pts (253 COMPASS and 212 IRCCS). Baseline characteristics were similar. The combined median age was 64 yrs (28, 84); 402 (86%) had metastatic PDAC and 63 (14%) locally advanced. 56 (12%) had prior surgery, 40 (9%) had prior adjuvant therapy. In total, 296 (64%) and 169 (36%) were GATA6 high and low respectively. OS in months (m) analyses by GATA6 expression are summarized (Table). We demonstrate no difference between OS based on primary tumor location (p=0.09), however, regardless of location, GATA6 high tumors show statistically significant better OS. We confirm, by interaction term, GATA6 as a predictive biomarker, with GATA6 high predictive of response to mFFX while low expression demonstrates less benefit with mFFX (p=0.003). Conclusions: GATA6 is a highly prognostic biomarker. We did not find an association with tumor location, which also was not prognostic in this study. Importantly GATA6 was predictive of survival in patients receiving mFFX, suggesting GATA6 low tumors should receive 1st line GnP based regimens. Clinical trial information: NCT02750657 . [Table: see text]
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 | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 ».