Yan Jianing, Ye Guoliang, Shao Yongfu, Zhou Hanxuan
Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo, China.
Department of Gastroenterology, Institute of Digestive Disease of Ningbo University, Ningbo, China.
Front Genet. 2023 Mar 29;14:1158341. doi: 10.3389/fgene.2023.1158341. eCollection 2023.
Hepatocellular carcinoma (HCC) remains notorious for its high malignancy, poor prognosis and high mortality. The exploration of novel therapeutic agents for HCC has remained challenging due to its complex aetiology. Therefore, it is necessary to elucidate the pathogenesis and mechanism of HCC for clinical intervention. We collected data from several public data portals and systematically analysed the association between transcription factors (TFs), eRNA-associated enhancers and downstream targets. We next filtered the prognostic genes and established a novel prognosis-related nomogram model. Moreover, we explored the potential mechanisms of the identified prognostic genes. The expression level was validated by several ways. We first constructed a significant TF-enhancer-target regulatory network and identified DAPK1 as a coregulatory differentially expressed prognosis-related gene. We combined common clinicopathological factors and built a prognostic nomogram model for HCC. We found that our regulatory network was correlated with the processes of synthesizing various substances. Moreover, we explored the role of DAPK1 in HCC and found that it was associated with immune cell infiltration and DNA methylation. Several immunostimulators and targeting drugs could be promising immune therapy targets. The tumor immune microenvironment was analyzed. Finally, the lower DAPK1 expression in HCC was validated the GEO database, UALCAN cohort, and qRT-PCR. In conclusion, we established a significant TF-enhancer-target regulatory network and identified downregulated DAPK1 as an important prognostic and diagnostic gene in HCC. Its potential biological functions and mechanisms were annotated using bioinformatics tools.
肝细胞癌（HCC）因其高恶性、预后差和高死亡率而一直臭名昭著。由于其病因复杂，探索用于HCC的新型治疗药物一直具有挑战性。因此，有必要阐明HCC的发病机制和机理以进行临床干预。我们从几个公共数据门户收集数据，并系统分析了转录因子（TFs）、与eRNA相关的增强子和下游靶点之间的关联。接下来，我们筛选了预后基因并建立了一个新的预后相关列线图模型。此外，我们探索了已鉴定的预后基因的潜在机制。通过多种方式验证了表达水平。我们首先构建了一个重要的TF-增强子-靶点调控网络，并将DAPK1鉴定为一个共调控差异表达的预后相关基因。我们结合常见的临床病理因素，构建了HCC的预后列线图模型。我们发现我们的调控网络与各种物质的合成过程相关。此外，我们探索了DAPK1在HCC中的作用，发现它与免疫细胞浸润和DNA甲基化有关。几种免疫刺激剂和靶向药物可能是有前景的免疫治疗靶点。分析了肿瘤免疫微环境。最后，通过GEO数据库、UALCAN队列和qRT-PCR验证了HCC中较低的DAPK1表达。总之，我们建立了一个重要的TF-增强子-靶点调控网络，并鉴定出下调的DAPK1是HCC中一个重要的预后和诊断基因。使用生物信息学工具注释了其潜在的生物学功能和机制。
