NFYA在肝细胞癌中的表达、预后及免疫特征的综合分析

Comprehensive analysis of the expression,prognosis,and immune profiles of NFYA in hepatocellular carcinoma

目的:基于公共数据库、体外细胞系和肿瘤组织分析核转录因子Y亚基A(nuclear transcription factor Y subunit A, NFYA)在肝细胞癌(hepatocellular carcinoma, HCC)中的表达和临床意义。方法:TCGA数据库获取HCC患者临床数据和转录组数据并进行分析,qRT-PCR和免疫组化染色法验证NFYA在HCC细胞系和患者组织中的表达。单因素和多因素Cox回归分析、Kaplan-Meier分析、GO和KEGG分析等方法分析NFYA表达水平与HCC患者临床病理特征、预后、潜在致病机制以及免疫细胞浸润等的相关性。结果:公共数据库分析显示NFYA mRNA在HCC组织中较正常肝组织表达显著增高,并且该现象在HCC细胞系中得到了验证;在研究者队列HCC组织中,NFYA蛋白表达量也显著高表达。NFYA mRNA表达水平与HCC患者组织学分级、T分期、病理学分期正相关;NFYA高表达的HCC患者预后更为不良;HCC中与NFYA相关的基因主要富集于核裂解、细胞周期等生物过程;肿瘤微环境分析提示NFYA高表达与较低的免疫细胞浸润及基质细胞浸润相关,且NFYA表达与多种免疫检查点基因表达呈正相关。结论:HCC患者高表达NFYA与预后不良相关,可作为HCC患者潜在的预后标志物,且可能通过影响细胞周期和免疫细胞浸润调控HCC发生发展。

Objective:To analyze the expression and clinical significance of nuclear transcription factor Y subunit A(NFYA)in hepatocellular carcinoma(HCC)based on public databases and studies in vitro cell lines and tumor tissues.Methods:Transcriptome and clinical data of HCC patients were obtained and analyzed from the TCGA database.The expression of NFYA in HCC cell lines and patient tissues was validated through qRT-PCR and immunohistochemical staining.The correlation between NFYA expression levels and clinical-pathological features, prognosis, potential pathogenic mechanisms and immune cell infiltrationwas analyzed using univariate and multifactorial Cox regression analysis, Kaplan-Meier analysis, GO and KEGG analysis. Re⁃sults: NFYA mRNA expression was significantly increased in HCC tissues compared to normal liver tissues, and this phenomenonwas also confirmed in HCC cell lines. In the study cohort of HCC tissues, NFYA protein expression was significantly upregulated.NFYA mRNA expression level was correlated with tumor histological grade, T stage, and pathological stage. HCC patientswith high NFYA expression had a worse prognosis. NFYA-related genes in HCC were mainly enriched in biological processessuch as nuclear cleavage and cell cycle.The analysis of the tumor microenvironment suggested that high NFYA expression wasassociated with lower immune cell infiltration and stromal cell infiltration, and that NFYA expression was positively correlatedwith the expression of multiple immune checkpoint genes. Conclusion: NFYA is overexpressed and associated with poor prognosisin HCC patients and may serve as a potential prognostic marker. This activity of NFYA in HCC might be related to its influenceon cell cycle and immune cell infiltration.