Abstract 4800: Heterogeneity of cancer associated fibroblasts in non-small cell lung cancer is defined by the level of collagen gel contraction activity
Notice bibliographique
Résumé
Abstract Background: Cancer associated fibroblasts (CAFs) are well known to strongly influence tumor development, progression and metastasis. Their characteristics and prognostic gene signature in non-small cell lung cancer (NSCLC) patients have been recognized. However, the functional heterogeneity of CAFs between patients and their genetic basis were far less known. The results revealed two functionally and also genetic distinct subgroups of CAFs which were closely related to the degree of tumor desmoplasia and also prognostic of survival in NSCLC patients. Methods: 28 independent lung cancer resection specimens were used to establish primary cultures of CAFs and noncancer fibroblasts from the corresponding nonneoplastic lung parenchyma. We applied collagen gel contraction and xCELLigence Real-Time Cell Analysis of proliferation and in vivo tumorigenicity for measuring the CAF activity. To assess the grading of desmoplasia, the percentage of desmoplasia in total tumor stroma was used to define high desmoplasia (HD) versus low desmoplasia (LD). Microarray data on RNA extracted from contracted gels following 8 hours incubation was performed using Illumina Human HT-12v4 Bead Chips array and was preprocessed and normalized using RMA and values were log2 transformed. Results: We have identified that CAF activity depends on higher ability to contract collagen gel, increased cell proliferation and tumor growth. Using microarray gene expression analysis of the 24 CAF cell lines (12 CAFs-HD versus 12 CAFs-LD), we observed high correlation of differential gene expression in extreme CAF-HD to tumor stroma while we found a high correlation between differential gene expression in extreme CAF-LD to normal lung. We were also able to validate our previous published subset of 11 genes (13 probe sets) in CAFs-HD versus CAFs-LD. To study the degree of desmoplasia and outcome, we used MedBio data set containing 181 records. We observed that desmoplasia appears to be associated with the time to relapse in univariable analysis. The association was far stronger in the adenocarcioma group with significance for both univariable and multivariable analysis. Conclusion: In this study, we provided the direct and robust evidence of functional heterogeneity of CAFs in NSCLC patients and first showed that CAFs from tumor with severe desmoplasia had higher gel contraction activity, proliferation rate and enhanced tumor growth. Furthermore, we developed desmoplasia-specific gene signature that could subgroup CAFs and contribute to their functional heterogeneity which would also allow us to discriminate among patients who would more likely benefit from tumor stroma targeting therapies in the future. Citation Format: Roya Navab, Jing Hao, Shingo Sakashita, Dennis Wang, Melania Pintilier, Yuhui Wang, Chang-Qi Zhu, Kalpana Venkat, Igor Jurisica, Ming-Sound Tsao. Heterogeneity of cancer associated fibroblasts in non-small cell lung cancer is defined by the level of collagen gel contraction activity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4800. doi:10.1158/1538-7445.AM2014-4800
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 | 0,000 | 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 ».