RESUMEN
BACKGROUND: Metabolic reprogramming is an emerging hallmark that influences the tumour microenvironment (TME) by regulating the behavior of cancer cells and immune cells. The relationship between metabolism and immunity remains elusive. The purpose of this study was to explore the predictive value of immune- and metabolism-related genes in hepatocellular carcinoma (HCC) and their intricate interplay with TME. METHODS: We established the immune- and metabolism-related signature (IMRPS) based on the LIHC cohort from The Cancer Genome Atlas (TCGA) dataset. Kaplan-Meier analysis, receiver operating characteristic (ROC) curve analysis and Cox regression analysis confirmed the prognostic value of IMRPS. We investigated differences in immune cell infiltration, clinical features, and therapeutic response between risk groups. The quantitative real-time PCR (qPCR) was used to confirm the expression of signature genes. Immunohistochemical staining was performed to evaluate immune infiltration features in HCC tissue samples. We conducted cell experiments including gene knockout, cell counting kit-8 (CCK-8), and flow cytometry to explore the role of the IMRPS key gene UCK2 in HCC. RNA-seq was used to further investigate the potential underlying mechanism involved. RESULTS: The IMRPS, composed of four genes, SMS, UCK2, PFKFB4 and MAPT, exhibited significant correlations with survival, immune cell infiltration, clinical features, immune checkpoints and therapeutic response. The IMRPS was shown to be an excellent predictor of HCC prognosis. It could stratify patients appropriately and characterize the TME accurately. The high-risk HCC group exhibited an immunosuppressive microenvironment with abundant M2-like macrophage infiltration, which was confirmed by the immunohistochemistry results. The results of qPCR revealed that the expression of signature genes in 20 HCC tissues was significantly greater than that in adjacent normal tissues. After the key gene UCK2 was knocked out, the proliferation of the Huh7 cell line was significantly inhibited, and monocyte-derived macrophages polarized towards an M1-like phenotype in the coculture system. RNA-seq and GSEA suggested that the phenotypes were closely related to the negative regulation of growth and regulation of macrophage chemotaxis. CONCLUSIONS: This study established a new IMRS for the accurate prediction of patient prognosis and the TME, which is also helpful for identifying new targets for the treatment of HCC.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Microambiente Tumoral , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/patología , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Pronóstico , Biomarcadores de Tumor/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Masculino , Persona de Mediana Edad , Perfilación de la Expresión Génica , TranscriptomaRESUMEN
Ilex viridis Champ. ex Benth. is domestic to southern China. In the present work, the complete chloroplast (cp) genome sequence of Ilex viridis was assembled and characterized by high-throughput sequencing analyses. The chloroplast genome was 157,701 bp in length, consisting of large single-copy (LSC) and small single-copy (SSC) regions of 87,177 bp and 18,394 bp, respectively, which were separated by a pair of 26,065 bp inverted repeat (IR) regions. The genome was predicted to contain 134 genes, including 89 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The overall GC content of the genome is 37.7%. The phylogenetic tree reconstructed using 13 chloroplast genomes reveals that I. viridis is mostly related to Ilex szechwanensis.
