■蛋白质精氨酸甲基转移酶(PRMT)家族成员在癌症过程中具有重要作用。然而,其在调节肝细胞癌(HCC)的癌症免疫治疗中的功能尚未完全了解。本研究旨在探讨PRMT1在HCC中的作用。
■获得单细胞RNA测序(scRNA-seq)和临床病理数据,并用于探索诊断和预后价值,PRMT1在HCC细胞功能和免疫微环境调节中的作用。使用京都基因和基因组百科全书(KEGG)和基因本体论(GO)探索PRMT1的功能,以及基因集富集分析(GSEA)。TIMER和CIBERSORT用于分析PRMT1表达与免疫细胞浸润之间的关系。STRING数据库用于构建蛋白质-蛋白质相互作用(PPI)网络。
■PRMT1在HCC中异常表达,高表达与肿瘤进展有关,HCC患者的总生存期(OS)和无病生存期(DFS)较差。PRMT1也与免疫细胞浸润有关。此外,它在免疫细胞中特异性表达,包括耗尽的CD8T细胞,B细胞,和免疫治疗患者的单/宏细胞。在HCC患者的高PRMT1表达组中,免疫检查点的表达显着增加。关于生物学机制,细胞活力,移民和入侵,PRMT1敲低肝癌细胞中脂肪酸代谢相关基因的表达受到抑制。此外,与PRMT1共表达的基因参与脂肪酸代谢过程,并在脂肪和药物诱导的肝病中富集。
■放在一起,这些结果表明,PRMT1可能通过免疫微环境调节和脂肪酸代谢在HCC中发挥其致癌作用。我们的发现将为进一步的研究奠定基础,并为肝癌的潜在临床治疗靶点提供依据。
UNASSIGNED: Protein arginine methyltransferase (PRMT) family members have important roles in cancer processes. However, its functions in the regulation of cancer immunotherapy of hepatocellular carcinoma (HCC) are incompletely understood. This study aimed to investigate the roles of PRMT1 in HCC.
UNASSIGNED: Single-cell RNA sequencing (scRNA-seq) and clinicopathological data were obtained and used to explore the diagnostic and prognostic value, cellular functions and roles in immune microenvironment regulation of PRMT1 in HCC. The functions of PRMT1 were explored using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), as well as gene set enrichment analysis (GSEA). TIMER and CIBERSORT were used to analyze the relationships between PRMT1 expression and immune cell infiltration. The STRING database was used to construct a protein-protein interaction (PPI) network.
UNASSIGNED: PRMT1 was aberrantly expressed in HCC, which high expression was associated with tumor progression, worse overall survival (OS) and disease-free survival (DFS) of patients with HCC. PRMT1 was also associated with immune cell infiltration. Moreover, it was specifically expressed in immune cells, including exhausted CD8 T cells, B cells, and mono/macro cells in patients with immunotherapy. The expression of immune checkpoints was significantly increased in the high-PRMT1 expression groups of HCC patients. Regarding biological mechanisms, cell viability, migration and invasion, and the expression of genes related to fatty acid metabolism were suppressed in PRMT1 knockdown HCC cells. Moreover, genes co-expressed with PRMT1 were involved in the fatty acid metabolic process and enriched in fatty and drug-induced liver disease.
UNASSIGNED: Taken together, these results indicate that PRMT1 might exert its oncogenic effects via immune microenvironment regulation and fatty acid metabolism in HCC. Our finding will provide a foundation for further studies and indicate a potential clinical therapeutic target for liver cancer.