Abstract 2834: Metastatic colorectal cancer: characterization of distinct histological growth patterns which demonstrate different response to current treatment regimes
Notice bibliographique
Résumé
Abstract Colorectal cancer (CRC) is the third most common cancer in North America, and the third leading cause of cancer-related death. About 50% of patients will be diagnosed with CRC liver metastasis (CRCLM) during the course of their disease. We have identified two major histological growth patterns (HGP) in CRCLM resected from patients. In the desmoplastic HGP (DHGP), the tumor cells are enclosed within a desmoplastic stromal ring, physically separating them from the normal liver tissue. In the replacement HGP (RHGP), the tumor cells replace normal hepatocytes without disrupting adjacent cells or structures within the liver parenchyma. We have recently shown that patients with RHGP lesions who received neoadjuvant bevacizumab plus chemotherapy had a worse pathological response and five-year overall survival. Our group has also shown that RHGP CRCLM is resistant to anti-angiogenic therapy due to it promoting vessel co-option as a means of tumor vascularization, rather than VEGF-dependent angiogenesis as seen in DHGP. However, the molecular mechanisms that drive the CRCLM HGPs remain unknown. This project aims to shed light on the biological processes that underlie the diversity of HGPs, with an emphasis on the key genes and pathways that support the RHGP. To test this, we have: Aim 1) performed RNAseq on chemonaïve RHGP and DHGP CRCLM lesions to identify pathways that are significantly upregulated in the RHGP. We have validated these genes via real-time PCR (RT-PCR), and a subset by immunohistochemistry (IHC). Aim 2) To further refine the RHGP gene signature and to examine the effects of cell-cell interactions on hepatocyte and tumor cell gene expression, individual cells have been isolated from distinct regions within RHGP CRCLM tissues using laser capture microdissection (LCM), followed by single-cell transcriptomics analyses. Our preliminary data have identified three major pathways with differentially expressed genes: i. cell motility, ii. cell junctions, and iii. ECM-receptor interactions, which are upregulated in RHGP relative to the DHGP and normal liver. A panel of RHGP-specific genes has been identified and validated via RT-PCR. We selected a subset of these genes and are performing IHC to further validate and locate their expression. We have also performed LCM and are in the process of performing transcriptomics analyses – the data will be presented. We expect to gain some insight into the mechanisms responsible for driving and/or maintaining the RHGP lesions. In the longer term, this work will result in identification of targets in the HGPs that will help stratify patients in terms of treatment. It would appear that we have fewer treatment options for the RHGP patients and it would be important to utilize the data to develop new treatment strategies for those patients. These new therapies would lead to further clinical trials. Citation Format: Vincent Palmieri, Anthoula Lazaris, Hussam Alamri, Abdellatif Amri, Nisreen Ibrahim, Pablo Zoroquiain, Peter Vermeulen, Peter Metrakos. Metastatic colorectal cancer: characterization of distinct histological growth patterns which demonstrate different response to current treatment regimes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2834. doi:10.1158/1538-7445.AM2017-2834
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 | 0,000 | 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 ».