Integrated Bioinformatics Analysis of Master Regulators in Anaplastic Thyroid Carcinoma

Abstract

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and rapidly lethal tumors. However, limited advances have been made to prolong the survival and to reduce the mortality over the last decades. Therefore, identifying the master regulators underlying ATC progression is desperately needed. In our present study, three datasets including GSE33630, GSE29265, and GSE65144 were retrieved from Gene Expression Omnibus with a total of 32 ATC samples and 78 normal thyroid tissues. A total of 1804 consistently changed differentially expressed genes (DEGs) were identified from three datasets. KEGG pathways enrichment suggested that upregulated DEGs were mainly enriched in ECM-receptor interaction, cell cycle, PI3K-Akt signaling pathway, focal adhesion, and p53 signaling pathway. Furthermore, key gene modules in PPI network were identified by Cytoscape plugin MCODE and they were mainly associated with DNA replication, cell cycle process, collagen fibril organization, and regulation of leukocyte migration. Additionally, TOP2A, CDK1, CCNB1, VEGFA, BIRC5, MAPK1, CCNA2, MAD2L1, CDC20, and BUB1 were identified as hub genes of the PPI network. Interestingly, module analysis showed that 8 out of 10 hub genes participated in Module 1 network and more than 70% genes of Module 2 consisted of collagen family members. Notably, transcription factors (TFs) regulatory network analysis indicated that E2F7, FOXM1, and NFYB were master regulators of Module 1, while CREB3L1 was the master regulator of Module 2. Experimental validation showed that CREB3L1, E2F7, and FOXM1 were significantly upregulated in ATC tissue and cell line when compared with normal thyroid group. In conclusion, the TFs regulatory network provided a more detail molecular mechanism underlying ATC occurrence and progression. TFs including E2F7, FOXM1, CREB3L1, and NFYB were likely to be master regulators of ATC progression, suggesting their potential role as molecular therapeutic targets in ATC treatment.

Identification of prognostic significance of BIRC5 in breast cancer using integrative bioinformatics analysis

“…After co-expression and correlation analysis using the Oncomine, bc-GenExMiner, and UCSC Xena web-based tools in the present study, we confirmed that CDC20 gene was positively correlated with BIRC5 expression. As a matter of fact, both CDC20 and BIRC5 were found to be co-expressed in lung adenocarcinoma, endometrial cancer, renal cell carcinoma, and thyroid carcinoma [31][32][33][34]. Given that cell cycle process is often coordinated with apoptotic proteins to maintain tissue homeostasis, silencing the expressions of cell cycle protein as well as anti-apoptotic proteins simultaneously could potentially lead to cell cycle arrest and reduce the proliferation of breast cancer cells.…”

<p>Identification and Validation of Novel Genes in Anaplastic Thyroid Carcinoma via Bioinformatics Analysis</p>

“…Pan's study indicated that the hub genes showed inconsistent trends in ATC tissues, which may be due to the heterogeneity between cell line data and tumor tissue data. 52 So, only three of the five genes screened were validated in cell lines. The inconsistent results should be understandable.…”

“…54 The top 10 DEGs with highest node degree were regarded as hub genes of ATC in Pan's study. 52 Hu's study did not do the screening with any of those screening methods. They simply get the top 10 hub genes by PPI network.…”

Precise engineering of Gemcitabine prodrug cocktails into single polymeric nanoparticles delivery for metastatic thyroid cancer cells

“…Thyroid malignancy is commonly derived from stem of the thyroid follicular cells from epithelial, which can be additionally divided into the well distinguished malignancy cells, poorly discriminated malignance, and anaplastic malignance tumor cells rendering to the cancer behaviors. A distinguished thyroid malignancy cell is presently treated via thyroidectomy, succeeding radioactive iodine (RAI) treatment and long-standing thyroid triggering suppression of hormone (Bi et al., 2019 ; Corrigan et al., 2019 ; Ljubas et al., 2019 ; Pan et al., 2019 ). Although a majority of thyroid cancers have a favorable prognosis, there are scarcely any effective therapeutic approaches for metastatic thyroid cancers (Galofré et al., 2014 ; Kim et al., 2018 ; Ishihara et al., 2019 ; Janz et al., 2019 ; Wang et al., 2019 ).…”