FCGR1A Serves as a Novel Biomarker and Correlates With Immune Infiltration in Four Cancer Types.

Ji-Li Xu,Yong Guo

doi:10.3389/fmolb.2020.581615

Ji-Li Xu, Yong Guo

Open Access

https://doi.org/10.3389/fmolb.2020.581615

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Abstract

BackgroundFCGR1A encodes a protein that plays an important role in the immune response. The prognostic impact and immune infiltration of FCGR1A in heterogeneous cancers remain unclear.MethodsDifferential expression of FCGR1A between tumor and normal tissues and the discrepancies in overall survival (OS) among diverse cancer types were performed by Gene Expression Profiling Interactive Analysis. The correlation between FCGR1A and immune cells or gene marker sets of immune infiltrates was analyzed via Tumor Immune Estimation Resource (TIMER). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and protein-to-protein interaction (PPI) network were used to explore the function and related genes of FCGR1A. The relationships among these genes were further analyzed by TIMER.ResultsFCGR1A is highly expressed in various cancer types. FCGR1A was significantly correlated with the OS of cervical and endocervical cancer (CESC), cholangiocarcinoma (CHOL), kidney renal clear cell carcinoma (KIRC), and skin cutaneous melanoma (SKCM) (P < 0.05). High expression of FCGR1A meant a better prognosis besides KIRC. FCGR1A showed significant differences at different stages of KIRC and SKCM (P < 0.05). Furthermore, FCGR1A was notably associated with infiltrating levels of CD4+ T cells, CD8+ T cells, B cells, macrophages, neutrophils, and dendritic cells in the four cancers (P < 0.05). FCGR1A also showed close relevance with different immune gene markers. The copy number variation of FCGR1A significantly influenced the abundance of immune infiltration in KIRC and SKCM. GO, KEGG analysis, and PPI network analysis revealed that FCGR1A is involved in many pathophysiological processes and was most related to FCGR3A. And this gene indicated highly significant positive correlations with FCGR1A in four cancers.ConclusionFCGR1A may be a potential prognostic biomarker and related to immune infiltration levels in diverse cancers, especially in CESC, CHOL, KIRC, and SKCM. Besides, FCGR1A may be involved in the activation, regulation, or induction of immune cells and diverse physiological and pathological processes.

Highlights

FCGR1A (CD64) is a 72-kDa transmembrane glycoprotein with CD32 and CD16 receptors (Kiyoshi et al, 2015; Lu and Sun, 2015)
To determine the differential expression of FCGR1A in various cancer locations, we used RNA-seq data from The Cancer Genome Atlas (TCGA) database to explore the relationship between prognosis and FCGR1A expression in multiple cancer types via Gene Expression Profiling Interactive Analysis (GEPIA)
Together with the above results, FCGR1A expression levels were significantly higher in bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), CESC, CHOL, colon adenocarcinoma (COAD), esophageal carcinoma (ESCA), glioblastoma multiforme (GBM), head and neck cancer (HNSC), serous cystadenocarcinoma (OV), pancreatic adenocarcinoma Kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), acute (PAAD), prostate adenocarcinoma (PRAD), rectum myeloid leukemia (LAML), lower-grade glioma (LGG), ovarian adenocarcinoma (READ), Skin cutaneous melanoma (SKCM), stomach adenocarcinoma

Summary

Introduction

FCGR1A (CD64) is a 72-kDa transmembrane glycoprotein with CD32 and CD16 receptors (Kiyoshi et al, 2015; Lu and Sun, 2015). It encodes a protein that plays an important role in both innate and adaptive immune response. FCGR1A is one of three related gene family members located on chromosome 1 and often expressed on the surface of monocytes, macrophages, and dendritic cells (DCs) (Hulett and Hogarth, 1998). CD64 is rarely expressed on the surface of neutrophils (PMN) in normal condition. When the body is infected, CD64 expression on the surface of neutrophils can be rapidly increased under the stimulation of bacterial lipopolysaccharide, interleukin, interferon-γ, and granulocyte colony-stimulating factor (Mangalam and Yadav, 2019). Neutrophils are often the first immune cells to reach sites of infection, and their main function is to phagocytose and destroy invading microorganisms or foreign material. FCGR1A encodes a protein that plays an important role in the immune response. The prognostic impact and immune infiltration of FCGR1A in heterogeneous cancers remain unclear

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