Identification of key candidate genes and pathways in follicular variant papillary thyroid carcinoma by integrated bioinformatical analysis

Lanyu Jing, Fada Xia, Xin Du, Bo Jiang, Yong Chen, Xinying Li


Background: Follicular variant papillary thyroid carcinoma (FVPTC) is a heterogeneous group of tumors that differ morphologically, genetically, and clinically. This study aimed to investigate the gene mutation and gene expression profiles, especially the pathways in the interaction network and the diagnostic approaches of candidate markers of FVPTC.
Methods: The clinicopathological characteristics, gene mutation types, and mRNA expression profiles of patients with FVPTC were studied utilizing the data downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) were identified, and functional enrichment analysis was applied. A protein-protein interaction (PPI) network was constructed to identify hub genes and receiver operating characteristic (ROC) analysis was used to evaluate candidate gene diagnostic values.
Results: RAS and BRAF mutations were the predominant mutation types in FVPTC. FVPTC was significantly correlated with the absence of extrathyroidal extension, lower N stage, and the low occurrence rate of BRAF mutation compared to classical PTC. Two thousand three hundred and forty-two FVPTC- related differentially expressed mRNAs (DEGs) and 420 FVPTC-specific DEGs were identified in this study. Function enrichment analysis revealed that these DEGs were involved in some pathways in cancer, including the PI3K-Akt signaling pathway and MAPK signaling pathways. The PPI network was constructed from 420 FVPTC-specific DEGs, and a sub-network, including 12 genes and 10 hub genes, was verified.
Conclusions: FVPTC was identified significantly relevant to remarkable alterations of gene mutation, DEGs, related pathways and the diagnostic performance of hub genes. Our study might provide further insights into the investigation of the tumorigenesis mechanism of FVPTC and assist in the discovery of new candidate diagnostic markers for FVPTC.

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