The correlation between immune subtypes and consensus molecular subtypes in colorectal cancer identifies novel tumour microenvironment profiles, with prognostic and therapeutic implications
Autor: | Rocio Garcia-Carbonero, Beatriz Gil-Calderón, Gonzalo Gómez-López, A. La Salvia, Fatima Al-Shahrour, Luis Álvarez-Vallina, M.C. Riesco, Carlos Carretero-Puche, J. Sarmentero, Beatriz Soldevilla, B. Rubio-Cuesta, P. Espinosa-Olarte, G. Gomez-Esteves |
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Přispěvatelé: | UAM. Departamento de Bioquímica |
Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Male Cancer Research Colorectal cancer medicine.medical_treatment Lymphocyte Consensus molecular subtypes Genes MHC Class I CD8-Positive T-Lymphocytes Monocytes Transcriptome 0302 clinical medicine Transforming Growth Factor beta Tumor Microenvironment Lymphocytes Wnt Signaling Pathway education.field_of_study Neovascularization Pathologic Inmunotherapy Prognosis Adenocarcinoma Mucinous medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Female Microsatellite Instability Immunotherapy Colorectal Neoplasms Signal Transduction Proto-Oncogene Proteins B-raf Immune subtypes Epithelial-Mesenchymal Transition Medicina Population Receptors Antigen T-Cell Adenocarcinoma Proto-Oncogene Proteins c-myc Proto-Oncogene Proteins p21(ras) 03 medical and health sciences Interferon-gamma Immune system Th2 Cells health services administration medicine Humans education Aged Cell Proliferation Inflammation Wound Healing business.industry Macrophages Th1 Cells medicine.disease 030104 developmental biology Cancer cell Cancer research Th17 Cells business CD8 Tumour microenviroment |
Zdroj: | Soldevilla, B, Carretero-Puche, C, Gomez-Lopez, G, Al-Shahrour, F, Riesco, M C, Gil-Calderon, B, Alvarez-Vallina, L, Espinosa-Olarte, P, Gomez-Esteves, G, Rubio-Cuesta, B, Sarmentero, J, La Salvia, A & Garcia-Carbonero, R 2019, ' The correlation between immune subtypes and consensus molecular subtypes in colorectal cancer identifies novel tumour microenvironment profiles, with prognostic and therapeutic implications ', European Journal of Cancer, vol. 123, pp. 118-129 . https://doi.org/10.1016/j.ejca.2019.09.008 Biblos-e Archivo. Repositorio Institucional de la UAM instname Biblos-e Archivo: Repositorio Institucional de la UAM Universidad Autónoma de Madrid |
Popis: | Background Solid tumour growth is the consequence of a complex interplay between cancer cells and their microenvironment. Recently, a new global transcriptomic immune classification of solid tumours has identified six immune subtypes (ISs) (C1–C6). Our aim was to specifically characterise ISs in colorectal cancer (CRC) and assess their interplay with the consensus molecular subtypes (CMSs). Methods Clinical and molecular information, including CMSs and ISs, were obtained from The Cancer Genome Atlas (TCGA) (N = 625). Immune cell populations, differential gene expression and gene set enrichment analysis were performed to characterise ISs in the global CRC population by using CMSs. Results Only 5 ISs were identified in CRC, predominantly C1 wound healing (77%) and C2 IFN-γ dominant (17%). CMS1 showed the highest proportion of C2 (53%), whereas C1 was particularly dominant in CMS2 (91%). CMS3 had the highest representation of C3 inflammatory (7%) and C4 lymphocyte depleted ISs (4%), whereas all C6 TGF-β dominant cases belonged to CMS4 (2.3%). Prognostic relevance of ISs in CRC substantially differed from that reported for the global TCGA, and ISs had a greater ability to stratify the prognosis of CRC patients than CMS classification. C2 had higher densities of CD8, CD4 activated, follicular helper T cells, regulatory T cells and neutrophils and the highest M1/M2 polarisation. C2 had a heightened activation of pathways related to the immune system, apoptosis and DNA repair, mTOR signalling and oxidative phosphorylation, whereas C1 was more dependent of metabolic pathways. Conclusions The correlation of IS and CMS allows a more precise categorisation of patients with relevant clinical and biological implications, which may be valuable tools to improve tailored therapeutic interventions in CRC patients. This work was funded by projects DTS15/00157 , PI16/01827 and CIBER-ONC CB16/12/00442 from the Instituto de Salud Carlos III ( Ministry of Economy, Industry and Competitiveness, Spain ) and cofunded by the European Regional Development Fund (ERDF, European Union), and approved by the Ethics Committee or our Institution. BS is funded by AECC (Spain). MCR is funded by Instituto de Salud Carlos III and SEOM (Spain) CCP and BRC are funded by CAM (Programa de Empleo Juvenil (YEI)) |
Databáze: | OpenAIRE |
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