NAP1L1 Functions as a Novel Prognostic Biomarker Associated With Macrophages and Promotes Tumor Progression by Influencing the Wnt/β-Catenin Pathway in Hepatocellular Carcinoma.

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.