Abstract B87: Co-expression of GLUT1 and MCT4 is a poor prognostic marker and predicts response to adjuvant chemotherapy in PDAC
Notice bibliographique
Résumé
Abstract Background: Mutant KRAS stimulates glucose uptake and lactate production in pancreatic ductal adenocarcinoma (PDAC), contributing to metabolic pathway reprogramming and tumor progression. A prognostic effect for glucose transporter GLUT1 and lactate transporter MCT4 expression in PDAC has been demonstrated but it is not known if the expression of markers of glycolytic and lactate metabolism pathways is predictive of treatment response. We aimed to validate the prognostic and assess the predictive effects of GLUT1 and MCT4 protein levels in resectable PDAC. Methods: Immunohistochemical analysis for GLUT1 and MCT4 was performed on a tissue microarray (TMA) comprising 261 resected PDAC tumors with associated clinical outcome data. The expression of GLUT1 and MCT4 in the epithelial compartment of PDAC was quantified and patient samples were scored as low (negative and weak staining) and high (moderate and strong staining) expression groups. Univariable disease-specific survival (DSS) was assessed using the Kaplan-Meier method. Results: 70% (182) of the patients included in the TMA had high GLUT1 staining and 58% had high MCT4 staining. GLUT1high patients had reduced median DSS compared to GLUT1low patients (1.34 vs. 2.05 years, p=0.0136). Median DSS was also reduced in the MCT4high group (1.33 vs. 1.91 years in MCT4low, p=0.0153). There was a significant co-occurrence of high GLUT1 with high MCT4 expression (70%, p<0.0001). GLUT1highMCT4high patients had reduced DSS (N=124, 1.21 years, p=0.0114) compared to GLUT1lowMCT4low (N=55, 2.04 years), GLUT1lowMCT4high (N=27, 2.12 years) and GLUT1highMCT4low (N=61, 1.85 years). 31% of all patients received adjuvant single agent chemotherapy with a pyrimidine analog. Two of the combined GLUT1/MCT4 phenotypes were found to be predictive biomarkers for adjuvant chemotherapy. GLUT1lowMCT4low showed a treatment associated two year increase in median DSS (3.32 vs. 1.38 years, p=0.0020) and GLUT1highMCT4high demonstrated a treatment associated 10 month increase in median DSS (1.68 vs. 0.89 years, p=0.0071) compared to no adjuvant therapy. No significant treatment related differences were observed in either the GLUT1lowMCT4high (p=0.24) or GLUT1highMCT4low groups (p=0.95). Conclusions: GLUT1 and MCT4 expression are poor prognostic markers in PDAC and co-expression of these biomarkers enhances this effect. Neither GLUT1 nor MCT4 were found to be of predictive relevance when considered individually. Patients with low tumor GLUT1 and MCT4 expression had the best outcomes with chemotherapy with a pyrimidine analog. Hence, immunohistochemical analysis of GLUT1 and MCT4 in resected PDAC defines patient subgroups with different survival prognosis and predicted sensitivity to pyrimidine analog chemotherapy. The combined effect of GLUT1 and MCT4 expression on PDAC outcome suggests that therapeutic agents which can alter the glycolytic/lactate pathway may have potential for increasing sensitivity to treatment. Citation Format: Joanna M. Karasinska, Steve E. Kalloger, Hui-li Wong, Taixiang Wang, Daniel J. Renouf, David F. Schaeffer.{Authors}. Co-expression of GLUT1 and MCT4 is a poor prognostic marker and predicts response to adjuvant chemotherapy in PDAC. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr B87.
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 | 0,000 | 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) | 0,004 | 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 ».