AUTHOR=Geng Qi-Shun , Huang Tao , Li Li-Feng , Shen Zhi-Bo , Xue Wen-Hua , Zhao Jie 

TITLE=Over-Expression and Prognostic Significance of FN1, Correlating With Immune Infiltrates in Thyroid Cancer

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2022

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.812278

DOI=10.3389/fmed.2021.812278

ISSN=2296-858X

ABSTRACT=<sec><title>Background</title><p>Thyroid cancer (THCA) is a malignancy affecting the endocrine system, which currently has no effective treatment due to a limited number of suitable drugs and prognostic markers.</p></sec><sec><title>Methods</title><p>Three Gene Expression Omnibus (GEO) datasets were selected to identify differentially expressed genes (DEGs) between THCA and normal thyroid samples using GEO2R tools of National Center for Biotechnology Information. We identified hub gene <italic>FN1</italic> using functional enrichment and protein-protein interaction network analyses. Subsequently, we evaluated the importance of gene expression on clinical prognosis using The Cancer Genome Atlas (TCGA) database and GEO datasets. MEXPRESS was used to investigate the correlation between gene expression and DNA methylation; the correlations between <italic>FN1</italic> and cancer immune infiltrates were investigated using CIBERSORT. In addition, we assessed the effect of silencing <italic>FN1</italic> expression, using an <italic>in vitro</italic> cellular model of THCA. Immunohistochemical(IHC) was used to elevate the correlation between <italic>CD276</italic> and <italic>FN1</italic>.</p></sec><sec><title>Results</title><p><italic>FN1</italic> expression was highly correlated with progression-free survival and moderately to strongly correlated with the infiltration levels of M2 macrophages and resting memory CD4+ T cells, as well as with <italic>CD276</italic> expression. We suggest promoter hypermethylation as the mechanism underlying the observed changes in <italic>FN1</italic> expression, as 20 CpG sites in 507 THCA cases in TCGA database showed a negative correlation with <italic>FN1</italic> expression. In addition, silencing <italic>FN1</italic> expression suppressed clonogenicity, motility, invasiveness, and the expression of CD276 <italic>in vitro</italic>. The correlation between FN1 and CD276 was further confirmed by immunohistochemical.</p></sec><sec><title>Conclusion</title><p>Our findings show that <italic>FN1</italic> expression levels correlate with prognosis and immune infiltration levels in THCA, suggesting that <italic>FN1</italic> expression be used as an immunity-related biomarker and therapeutic target in THCA.</p></sec>