Colorectal cancer liver metastasis histological growth patterns; the role of the immune system
Notice bibliographique
Résumé
Background: Colorectal cancer (CRC) is amongst the three most common cancers worldwide. The majority of patients presenting with liver metastases (LM). Resection of liver lesions is the only curative measure. Unfortunately, less than 30% of patients are eligible for resection. Three major histological growth patterns (HGPs) have been identified in patients with colorectal cancer liver metastasis (CRCLM); desmoplastic, pushing and replacement. Patients with replacement lesions have a poor overall survival rate compared to those with desmoplastic when treated. A number of studies have reported that the magnitude of T-lymphocyte infiltration in CRCLM is significantly correlated with prognosis. High infiltration of macrophages has also been associated with better outcome. Furthermore, the role of these immune components when LM are segregated by HGP has not yet been evaluated thoroughly. Defining this is important in light of the fact that new therapies are based on manipulation of various components of the immune system. Methodology Gene Expression Analysis: Samples were obtained through the McGill University Hospital Centre Liver Disease Biobank; 9 Desmoplastic and 7 Replacement lesions. To minimize heterogeneity in the data, we selected chemonaïve samples. Samples were scored with our pathologist collaborators. Tumors were macrodissected, along with adjacent normal liver and processed Sequencing was performed by our collaborator Dr. Woong-Yang Park at the Samsung Genome Centre in South Korea, using the illumine HISeq sequencers. R© software was used to identify differentially expressed genes, and to generate heatmaps. From the output data, we studyied genes and pathways using Ingenuity Pathway Analysis © software.Immune Cell Quantification: Serial sections of formalin fixed paraffin embedded biopsies from CRCLM of both desmoplastic and replacement HGPs were stained via immunofluorescence, to assess the presence and distribution of various subtypes of T-lymphocytes and macrophages. Antibodies used were: CD68 (all macrophages), IRF5 (M1 macrophages), CMAF (M2 macrophages). Granzyme B (activated cytotoxic T-lymphocytes), CD4 (helper T-lymphocytes), and FOXP3 (regulatory T-lymphocytes). Tiled images of the whole tissue sections were obtained using a florescent microscope, followed by manual counting of each of the immune cell populations.ResultsGene Expression Analysis: Significant biological functions between the patterns consisted of those mostly related to cellular processes such as survival and invasion, suggesting that genes differentially expressed are those related to the tumor formation and metastases cascade. Furthermore, various genes that are related to immunological functions are mostly activated in the replacement pattern and conversely undetected in the desmoplastic subtypes.Immune Cell Quantification: The majority of immune cell populations concentrated at the tumor/liver interface in both growth patterns, whether that be the tumor peripheries, the desmoplastic ring, or the adjacent normal livers. Furthermore, when comparing desmoplastic and replacement patterns, we found that immune cells are mostly higher at the tumor/liver interface of the replacement pattern. We have also identified a rare subtype of immune cells; CD4- regulatory T-lymphocytes. This population has not yet been described in patients with CRC or with CRCLM.Conclusions: Different components of the immune system play diverse roles in the desmoplastic and replacement patterns of CRCLM. The findings described in this paper are new and will help increase our understanding of the diversity of CRC liver metastases. Such findings can direct future work to identity new prognostic markers and to help future therapeutics development towards therapies that can manipulate various components of the immune system.
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) | 0,003 | 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 ».