Abstract
Purpose: The accumulation of malignant tumor gene mutations makes differentiated thyroid cancer (DTC) gradually dedifferentiated to poorly differentiated thyroid cancer (PDTC) or anaplastic thyroid cancer (ATC). This study analyzed the gene expression profile in the process of dedifferentiation of thyroid cancer, aiming to explore the molecular mechanism of PDTC and ATC.Methods: Eight series from GEO database are collected for differentially expressed genes (DEGs) of DTC, PDTC and ATC. Then, GO analysis, KEGG pathway analysis, and functional path enrichment analyses are performed by MATESCAPE. Hub-genes are identified by using the method of MNC in protein interaction networks. Moreover, the expression of hub-genes and hub-gene related survival in thyroid cancers are analyzed by GEPIA2. Finally, the functional path enrichment pathways of PDTC are performed by GSEA Java.Results: There are obvious differences among DEGs of DTC, PDTC, and ATC, and 17 cross gene of DEGs were found. The DEGs in PDTC were mainly concentrated in regulation of cytoskeleton organization, cell division, positive regulation of kinase activity. While the DEGs in ATC were mainly in extracellular matrix organization, extracellular structure organization. Furthermore, 6 hub-genes were obtained in the development of PDTC by using Cytoscape: EGF, CCND1, DEPDC1, ANLN, HGF, BCL2L1. The high expression levels of the genes of EGF, DEPDC1, ANLN, HGF were associated with the poor survival of thyroid cancer. While the high expression levels of CCND1 and BCL2L1 were beneficial to the survival of patients with thyroid tumor. Finally, GSEA revealed that two gene sets are significantly enriched, including KEGG_THYROID_CANCER and KEGG_GLIOMA. And CCND1 and EGF have a core gene position in KEGG_GLIOMA.Conclusions: The molecular function (MF), biological processes (BP) and KEGG pathways have changed during the process of malignant transformation of thyroid cancer. Especially, the activation of EGF-EGFR pathway promotes the malignant transformation of thyroid tumor. Furthermore, six hub-genes, especially CCND1 and EGF, could become potential biomarkers of PDTC. This study can serve as a reference to understand the malignant transformation of thyroid cancer.
Bioinformatic analysis and identification of potential hallmarks in poorly differentiated thyroid cancer
