Abstract 2777: LOXL4-expressing neutrophils are found in colorectal cancer liver metastases resistant to anti-angiogenic therapy
Notice bibliographique
Résumé
Three different histopathological growth patterns (HGP) have been identified in colorectal cancer liver metastases (CRCLM) resected from patients: the desmoplastic HGP, the pushing HGP, and the replacement HGP. Evidence suggests that the predominant growth pattern with which a CRCLM presents has clinically relevant prognostic implications. We have shown that patients with replacement HGP lesions who received bevacizumab plus chemotherapy had a worse pathological response and five-year overall survival than those with desmoplastic HGP lesions receiving the same treatment. We have also demonstrated that CRCLM with the replacement HGP promote vessel co-option for vascularization, rather than sprouting angiogenesis as seen in desmoplastic HGP metastases. These findings point to the growth patterns in CRCLM possibly serving as predictive biomarkers of response to anti-angiogenic therapy, when no such biomarker has been validated to date. However, HGP scoring is performed on resected liver metastatic tissue, implying that preoperative treatment precedes growth pattern assessment. Therefore, surrogate markers for the HGPs that can be appraised prior to surgery would be helpful to inform clinical decision-making about whether a patient with CRCLM may benefit from anti-angiogenic treatment.This project aims to identify genes that are differentially expressed between CRCLM presenting with either the replacement or desmoplastic HGP. RNA sequencing (RNA-Seq) was used to compare the transcriptional profiles of these distinct CRCLM. A gene expression signature was generated from the RNA-Seq data to include genes that were upregulated in the replacement HGP liver metastases. Immunostaining of select genes from this signature was performed to validate these findings on human tumor tissue.Initial analysis of our RNA-Seq data identified 525 genes that are differentially expressed between the replacement and desmoplastic HGP CRCLM, of which 53 genes met the criteria for the gene expression signature. Pathway analysis of these genes identified pathways involved in the immune system and extracellular matrix (ECM) to be upregulated in the replacement HGP lesions. Subsequent immunostaining revealed the expression pattern of lysyl oxidase like-4 (LOXL4) protein to be distinct between the HGPs - significantly greater quantities of LOXL4-expressing neutrophils were detected in the replacement HGP tumor microenvironment.Characterizing differences in gene expression between replacement and desmoplastic HGP CRCLM is expected to provide some insight into the mechanisms responsible for generating these distinct growth patterns. Our findings suggest that further investigations into the role of tumor-associated leukocytes and ECM remodelling may ultimately lead to the development of biomarkers and new therapeutic targets for replacement HGP CRCLM.Citation Format: Vincent Palmieri, Anthoula Lazaris, Stephanie Petrillo, Hussam Alamri, Abdellatif Amri, Woong-Yang Park, Zu-hua Gao, Peter Metrakos. LOXL4-expressing neutrophils are found in colorectal cancer liver metastases resistant to anti-angiogenic therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2777.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| 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) | 0,000 | 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 tête enseignante, 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 ».