AUTHOR=Yang Bo , Zhao Yonghui , Wang Lan , Zhao Yuanyuan , Wei Lai , Chen Dong , Chen Zhishui 

TITLE=Identification of PLOD Family Genes as Novel Prognostic Biomarkers for Hepatocellular Carcinoma

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.01695

DOI=10.3389/fonc.2020.01695

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Hepatocellular carcinoma (HCC) is one of the most common malignancies with rising incidence and persistently high mortality. Previous researches have demonstrated that some <italic>PLOD</italic> family members are associated with tumor progression and metastasis in most human cancers. However, the prognostic and biological roles of <italic>PLODs</italic> in HCC remain largely unknown.</p></sec><sec><title>Methods</title><p>ONCOMINE, HPA, UALCAN, GEPIA, cBioPortal, GeneMANIA, NetworkAnalyst, Metascape, DAVID 6.8, and TIMER were used to determine the prognostic values and biological function of <italic>PLOD</italic> family members in HCC.</p></sec><sec><title>Results</title><p>The mRNA and protein expression patterns of <italic>PLOD</italic> family members were noticeably upregulated in HCC compared to normal tissue. The high expression levels of <italic>PLOD1</italic> and <italic>PLOD2</italic> genes were significantly correlated with higher tumor grades in HCC patients. In addition, the high expression levels of <italic>PLOD1–3</italic> were remarkably associated with poor overall survival in HCC patients, while high <italic>PLOD1</italic> and <italic>PLOD3</italic> expression were markedly associated with worse disease-free survival. In the co-expression gene analysis, 20 genes were primarily associated with the differentially expressed <italic>PLOD</italic> family members in HCC cases. Through functional enrichment analysis, the biological functions of <italic>PLODs</italic> in HCC were mainly involved in collagen fibril organization, lysine degradation, collagen biosynthesis, and modifying enzymes. Furthermore, the expression levels of <italic>PLOD1–3</italic> were positively correlated with the activities of tumor-infiltrating immune cells, including macrophages, neutrophils, CD4+ T cells, and dendritic cells. Besides, the expression levels of <italic>PLOD2</italic> and <italic>PLOD3</italic> were positively correlated with the infiltrating levels of B cells.</p></sec><sec><title>Conclusion</title><p>The findings of this study could provide novel insights into the identification of prognostic biomarkers for HCC patients.</p></sec>