Abstract
BackgroundThyroid 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.MethodsThree 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 FN1 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 FN1 and cancer immune infiltrates were investigated using CIBERSORT. In addition, we assessed the effect of silencing FN1 expression, using an in vitro cellular model of THCA. Immunohistochemical(IHC) was used to elevate the correlation between CD276 and FN1.ResultsFN1 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 CD276 expression. We suggest promoter hypermethylation as the mechanism underlying the observed changes in FN1 expression, as 20 CpG sites in 507 THCA cases in TCGA database showed a negative correlation with FN1 expression. In addition, silencing FN1 expression suppressed clonogenicity, motility, invasiveness, and the expression of CD276 in vitro. The correlation between FN1 and CD276 was further confirmed by immunohistochemical.ConclusionOur findings show that FN1 expression levels correlate with prognosis and immune infiltration levels in THCA, suggesting that FN1 expression be used as an immunity-related biomarker and therapeutic target in THCA.
Highlights
Thyroid carcinoma (THCA) is the most common type of endocrine cancer [1]
Gene Ontology (GO) analysis showed that the common Differentially Expressed Genes (DEGs) were mainly enriched in the cellular component (CC) category, including the plasma membrane, extracellular exosome, extracellular region, and extracellular space
DEGs annotated as biological process (BP) were enriched in cell adhesion, signal transduction, extracellular matrix organization, positive regulation of gene expression, positive regulation of cell proliferation, blood coagulation, wound healing, platelet degranulation, and nervous system development, all of which are processes associated with the occurrence and development of tumors
Summary
Thyroid carcinoma (THCA) is the most common type of endocrine cancer [1]. Its prevalence has sharply increased in recent decades. In the US, the annual incidence of thyroid cancer increased from 4.9/100,000 in 1975 to 14.3/100,000 in 2009 [2]. The most common treatment of thyroid cancer consists of surgical resection combined with radiotherapy or chemotherapy. For PTC, ATC, and MTC, a satisfactory resection is not always feasible, and even after radiotherapy, the risk of cancer recurrence is still high [5, 6]. The survival rate of patients with thyroid cancer is very high, with the rapid increase in THCA incidence, this disease poses a serious threat to human health [7]. 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
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