Identification of Biomarkers Related To The Diagnosis And Prognosis of Thyroid Cancer Through Bioinformatics Analysis
Abstract Background: Thyroid cancer is the most common malignant tumor of the head and neck. In recent years, the incidence of thyroid cancer (THCA) worldwide has rapidly increased and shows a trend in the younger generation. This study attempted to screen key genes and potential prognostic biomarkers for thyroid cancer using bioinformatics analysis.Methods: This study attempted to screen key genes and potential prognostic biomarkers for thyroid cancer using bioinformatics analysis. 101 cases of thyroid cancer and 78 cases of normal thyroid tissue were collected from three Gene Expression Omnibus (GEO) databases, then we identified the differentially expressed genes (DEGs) and conducted downstream analyses. Moreover, we screened hub genes by constructing a protein‐protein interaction (PPI) network. Finally, we assessed the expression level of hub genes in thyroid cancer tissue and its normal tissue using GEPIA and qRT-PCR respectively. Results: 159 upregulated and 251 downregulated genes were determined after gene integration of these three GEO data sets. Through PPI analysis, we consider the top 20 DEGs with high connectivity as the hub genes of THCA. After that, this study verified 20 central genes through the GEPIA database and found that only four hub genes (TOP2A, FN1, TIMP1, and MMP9) had significantly higher expression levels in thyroid cancer tissues than in normal thyroid tissues. We further analyzed the correlation between these four hub genes and the prognosis of patients with thyroid cancer, which suggests that FN1, MMP9, TIMP1 help assess the prognosis of patients with thyroid cancer. We performed GSEA analysis on these 4 hub genes simultaneously, found that the high expression of these 4 hub genes enriched the "cell cycle." Subsequently, we collected thyroid cancer tissue specimens, verified these four hub gene expression levels by RT-PCR, and found that only FN1 and TIMP1 genes in thyroid cancer tissues had significantly higher mRNA levels than normal tissues. Conclusions: Our research has identified 20 hub genes that may be related to the occurrence and development of thyroid cancer through multiple gene expression profile data sets and a series of comprehensive bioinformatics analyses. Further database and tissue validation analysis revealed that only 2 hub genes may be considered as potential prognostic biomarkers, including FN1 and TIMP1. In addition, these two hub genes are involved in the cell cycle, suggesting that they may play a role in the occurrence and development of thyroid cancer.