RESUMO
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-ß 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.
Assuntos
Adenocarcinoma Mucinoso/classificação , Adenocarcinoma/classificação , Neoplasias Colorretais/classificação , Adenocarcinoma/genética , Adenocarcinoma/imunologia , Adenocarcinoma/metabolismo , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/imunologia , Adenocarcinoma Mucinoso/metabolismo , Idoso , Linfócitos T CD8-Positivos , Proliferação de Células/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/metabolismo , Transição Epitelial-Mesenquimal/genética , Feminino , Genes MHC Classe I/genética , Humanos , Inflamação/imunologia , Interferon gama/imunologia , Linfócitos/imunologia , Linfócitos/metabolismo , Macrófagos/imunologia , Masculino , Instabilidade de Microssatélites , Monócitos/imunologia , Monócitos/metabolismo , Neovascularização Patológica , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Receptores de Antígenos de Linfócitos T/genética , Transdução de Sinais , Células Th1/imunologia , Células Th17/imunologia , Células Th2/imunologia , Fator de Crescimento Transformador beta/imunologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Via de Sinalização Wnt/genética , Cicatrização/genética , Cicatrização/imunologiaRESUMO
OBJECTIVES: Our goal was to evaluate the results of the first 100 liver transplants performed in our institution. METHODS: We retrospectively analyzed the first 100 liver transplants undertaken in adults from November 2001 to August 2005. RESULTS: The mean age of the recipients was 50 years (20 to 69) and 73% were men. The mean waiting time was 35 days. The mean age of the donors was 60 years (15 to 87), and 60% were men. One-year patient and graft survival rates were 93% and 90%, respectively. Three-year patient and graft survival rates were 85% and 82%, respectively. The need for retransplantation was 3%. Surgical complications included hepatic artery stenoses, 2%; hepatic artery thromboses, 2%; biliary leaks, 6%; and biliary stenoses, 14%. CONCLUSIONS: These results are no different from the overall results for liver transplantation in Spain during the same period.
