RESUMO
Macrophages, as essential components of the tumor immune microenvironment (TIME), could promote growth and invasion in many cancers. However, the role of macrophages in tumor microenvironment (TME) and immunotherapy in PCa is largely unexplored at present. Here, we investigated the roles of macrophage-related genes in molecular stratification, prognosis, TME, and immunotherapeutic response in PCa. Public databases provided single-cell RNA sequencing (scRNA-seq) and bulk RNAseq data. Using the Seurat R package, scRNA-seq data was processed and macrophage clusters were identified automatically and manually. Using the CellChat R package, intercellular communication analysis revealed that tumor-associated macrophages (TAMs) interact with other cells in the PCa TME primarily through MIF - (CD74+CXCR4) and MIF - (CD74+CD44) ligand-receptor pairs. We constructed coexpression networks of macrophages using the WGCNA to identify macrophage-related genes. Using the R package ConsensusClusterPlus, unsupervised hierarchical clustering analysis identified two distinct macrophage-associated subtypes, which have significantly different pathway activation status, TIME, and immunotherapeutic efficacy. Next, an 8-gene macrophage-related risk signature (MRS) was established through the LASSO Cox regression analysis with 10-fold cross-validation, and the performance of the MRS was validated in eight external PCa cohorts. The high-risk group had more active immune-related functions, more infiltrating immune cells, higher HLA and immune checkpoint gene expression, higher immune scores, and lower TIDE scores. Finally, the NCF4 gene has been identified as the hub gene in MRS using the "mgeneSim" function.
Assuntos
Antígenos de Histocompatibilidade Classe II , Oxirredutases Intramoleculares , Fatores Inibidores da Migração de Macrófagos , Neoplasias da Próstata , Análise de Sequência de RNA , Análise de Célula Única , Microambiente Tumoral , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Macrófagos/metabolismo , Macrófagos/imunologia , Regulação Neoplásica da Expressão Gênica , Prognóstico , Imunoterapia , Redes Reguladoras de Genes , Antígenos de Diferenciação de Linfócitos B/genética , Antígenos de Diferenciação de Linfócitos B/metabolismoRESUMO
OBJECTIVE: To evaluate the effect of health education on lung function and quality of life in stabilized patients with chronic pulmonary disease (COPD). METHODS: 117 stabilized COPD patients were randomly devided into 4 groups with numbers as 31,26, 20 and 40 identified as Groups 1 to 4. Patients in Group 1 did not receive health education, but Groups 2,3 and 4 received one, two, three or more times health education in file. FEV1, FEV1%, FEV1/FVC and SGRQ score were compared pre and 6-month post the health education program. RESULTS: Health education seemed successful in delaying the decline of FEV1, FEV%, FEV1/FVC and groups 2-4 were superior to group 1(P < 0.05) while groups 3 and 4 were superior to groups 1 or 2(P < 0.05). Health education was effective in raising the SGRQ score among the stabilized COPD patients with groups 2-4 superior to group 1 (P < 0.05) while groups 3 and 4 superior to groups 1 or 2 (P < 0.05). CONCLUSION: Health education could effectively delay the decline of both lung function and quality of life in stabilized patients with COPD.
