Integrated single-cell and bulk RNA sequencing analysis revealing the role of FCGR2A on prognosis and immune infiltration of hepatocellular carcinoma

Abstract

Abstract Objective To assess potential prognostic biomarkers of hepatocellular carcinoma (HCC) and preliminarily investigate their immune-related functions.Methods The CIBERSORT and ESTIMATE computational methods were applied to analyze the tumor microenvironment (TME) using the transcriptome and clinical data of HCC from The Cancer Genome Atlas (TCGA) database. The target gene was screened by intersecting the PPI network with Univariate Cox Regression Analysis. The distribution of the target gene expression in tumor-infiltrating immune cells (TICs) and immunological function were explored. Quality control, principal component analysis, TSNE clustering analysis, and cell annotation were also performed after downloading the single-cell RNA-sequencing data from the NCBI-GEO database. Lastly, we analyzed the distribution of the target gene at the single-cell level and established a comprehensive network of immune-related functions.Results Of the five hub genes (MMP9, FCGR2A, TLR2, CCR1 and PLAUR), FCGR2A was identified as the target gene following intersection analysis. It was up-regulated in tumor tissues and associated with poor prognosis of HCC patients. TSNE clustering study yielded 35 clusters, with hepatocyte, T cell, NK cell, macrophage, monocyte, B cell, smooth muscle cell, and endothelial cell as the result of annotation. Two of the results were related to immunological function. CIBERSORT analysis for the proportion of TICs revealed an increase in eosinophil number in tissues with low expression of FCGR2A. At the single-cell level, FCGR2A was mainly distributed in macrophages and monocytes.Conclusion This study showed that FCGR2A had an immunological role in the mono-macrophage system, was a promising biomarker for poor survival and could be a novel therapeutic target for HCC.