Shen Bingbing, Zhu Wenjie, Liu Xinyuan, Jiang Jianxin
Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
Department of Hepatic-Biliary-Pancreatic Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
Front Genet. 2022 May 19;13:876253. doi: 10.3389/fgene.2022.876253. eCollection 2022.
Hepatocellular carcinoma (HCC) is regarded as one of the universal cancers in the world. Therefore, our study is based on clinical, molecular mechanism and immunological perspectives to analyze how affects the progression of HCC. To begin with, the gene expression datasets and clinical data of GSE14520, GSE76427, ICGC, and TCGA are originated from GEO, ICGC, and TCGA databases. Subsequently, DEG screening was performed on data using R studio, and we finally found that 2,145 overlapping DEGs were screened from four datasets at the end. Then, we used R studio to filter the survival-related genes of the GSE76427 and ICGC datasets, and we screened out 101 survival-related genes. Finally, 33 common genes were screened out from 2,145 overlapping DEGs and 101 survival-related genes. Then, was screened from 33 common genes using the CytoHubba plug-in in Cytoscape software. Furthermore, ground on GEO, ICGC, and TCGA databases, the survival analysis, clinical feature analysis, univariate/multivariate regression analysis, and multiple GSEA were used to study NAP1L1. The Conclusion claimed that HCC patients with higher expression levels of NAP1L1 had a poorer prognosis than those with lower expression levels. Thus, we believe that is an independent prognostic factor for HCC. In order to shed light on NAP1L1's molecular mechanism promoting the progression of HCC closely, the GSEA tool was applied to complete the GSEA of the four datasets. Furthermore, the results confirmed that could promote HCC progression by regulating the G2/M transition of the cell cycle and signaling pathway. Western blot and flow cytometry were also performed to understand those mechanisms in this study. The result of Western blot showed that silencing led to downregulation of and proteins; the result of flow cytometry showed that cell numbers in the G2 phase were significantly increased when was silenced. Thus, we claimed that might promote HCC progression by activating the signaling pathway and promoting cell cycle G2/M transition. In addition, ground on GSE14520 and GSE76427 datasets, and ICGC and TCGA databases, the correlation between and immune cells was analyzed in HCC patients. At the same time, the TISIDB online database and the TIMER online database were testified to the association between and immune cells. Hence, the summary shows that was connected with a certain amount of immune cells. We can speculate that may influence macrophages to promote HCC progression through some potential mechanisms.
肝细胞癌（HCC）被认为是全球常见的癌症之一。因此，我们的研究基于临床、分子机制和免疫学视角，来分析[具体内容缺失]如何影响HCC的进展。首先，GSE14520、GSE76427、ICGC和TCGA的基因表达数据集及临床数据源自GEO、ICGC和TCGA数据库。随后，使用R studio对数据进行差异表达基因（DEG）筛选，最终我们从四个数据集中筛选出了2145个重叠的DEG。然后，我们使用R studio对GSE76427和ICGC数据集的生存相关基因进行筛选，筛选出101个生存相关基因。最后，从2145个重叠的DEG和101个生存相关基因中筛选出33个共同基因。接着，使用Cytoscape软件中的CytoHubba插件从33个共同基因中筛选出[具体内容缺失]。此外，基于GEO、ICGC和TCGA数据库，采用生存分析、临床特征分析、单因素/多因素回归分析以及多重基因集富集分析（GSEA）来研究NAP1L1。结论表明，NAP1L1表达水平较高的HCC患者预后比表达水平较低的患者更差。因此，我们认为[具体内容缺失]是HCC的一个独立预后因素。为了深入了解NAP1L1促进HCC进展的分子机制，应用GSEA工具对四个数据集进行GSEA分析。此外，结果证实[具体内容缺失]可通过调节细胞周期的G2/M转换和[具体信号通路缺失]信号通路来促进HCC进展。本研究还进行了蛋白质免疫印迹法（Western blot）和流式细胞术以了解这些机制。Western blot结果显示，[具体内容缺失]沉默导致[相关蛋白缺失]和[相关蛋白缺失]蛋白表达下调；流式细胞术结果显示，[具体内容缺失]沉默时G2期细胞数量显著增加。因此，我们认为[具体内容缺失]可能通过激活[具体信号通路缺失]信号通路并促进细胞周期G2/M转换来促进HCC进展。此外，基于GSE14520和GSE76427数据集以及ICGC和TCGA数据库，分析了HCC患者中[具体内容缺失]与免疫细胞之间的相关性。同时，通过TISIDB在线数据库和TIMER在线数据库验证了[具体内容缺失]与免疫细胞之间的关联。因此，总结表明[具体内容缺失]与一定数量的免疫细胞有关。我们可以推测，[具体内容缺失]可能通过某些潜在机制影响巨噬细胞以促进HCC进展。
