AUTHOR=Tan Siyou , Chen Wenyan , Kong Gaoyin , Wei Lai 

TITLE=ASPM May be Related to the Malignant Progression of Hepatitis B and is Associated With a Poor Prognosis of Hepatocellular Carcinoma

JOURNAL=Frontiers in Bioinformatics

VOLUME=2

YEAR=2022

URL=https://www.frontiersin.org/journals/bioinformatics/articles/10.3389/fbinf.2022.871027

DOI=10.3389/fbinf.2022.871027

ISSN=2673-7647

ABSTRACT=<p><bold>Background:</bold> Hepatitis B virus (HBV) is a causative agent of hepatocellular carcinoma (HCC). Until now, the mechanism behind the progress of hepatitis B fibrosis to HCC remains largely unknown. This study aims to examine the candidate biomarkers and pathways involved in HBV-associated HCC.</p><p><bold>Methods:</bold> Gene expression profiles were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the GEO2R tool after which functional enrichment analysis, protein-protein interaction (PPI) analysis, genetic alteration analysis, prognostic analysis, immune infiltration analysis, co-expression genes prediction, and miRNA-gene network construction, and pathway correlation analysis were performed.</p><p><bold>Results:</bold> 22 hub genes were identified, which were all highly expressed in HCC, and overexpression of these genes was all associated with significantly worse survival in HCC patients. More significantly, <italic>ASPM</italic> also showed increased expression levels in non-tumor tissues with advanced liver fibrosis. With the progression of liver fibrosis and the closer tumor center of HCC, the higher expression of <italic>ASPM</italic> was identified. <italic>ASPM</italic> was considered to be the most promising biomarker because it also showed the highest genetic alteration frequency among the hub genes and the expression level of <italic>ASPM</italic> in HBV (+) HCC tissues was significantly higher than that in HBV (-) HCC tissues. Also, the infiltration levels of B cells, CD8<sup>+</sup> T cells, CD4<sup>+</sup> T cells, macrophages, neutrophils, and dendritic cells were all positively correlated with the expression of <italic>ASPM</italic>.</p><p><bold>Conclusion:</bold> These findings may help in the development of strategies and candidate drugs for the treatment of HBV-related HCC and improve the effectiveness of personalized treatment in the future. <italic>ASPM</italic> was upregulated in both hepatitis B cirrhosis and HCC and could be a potential predicting biomarker.</p>