scholarly journals Bioinformatic analysis and identification of potential hallmarks in poorly differentiated thyroid cancer

Author(s):  
Xin Chen ◽  
Runsheng Ma ◽  
Hongqiang Li ◽  
Yifeng Tang ◽  
Detao Yin

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.

2016 ◽  
Vol 23 (3) ◽  
pp. R143-R155 ◽  
Author(s):  
Rengyun Liu ◽  
Mingzhao Xing

The 2013 discovery of Telomerase reverse transcriptase (TERT) promoter mutations chr5, 1,295,228 C>T (C228T) and 1,295,250 C>T (C250T) in thyroid cancer represents an important event in the thyroid cancer field and much progress has occurred since then. This article provides a comprehensive review of this exciting new thyroid cancer field. The oncogenic role of TERT promoter mutations involves their creation of consensus binding sites for E-twenty-six transcriptional factors. TERT C228T is far more common than TERT C250T and their collective prevalence is, on average, 0, 11.3, 17.1, 43.2 and 40.1% in benign thyroid tumors, papillary thyroid cancer (PTC), follicular thyroid cancer, poorly differentiated thyroid cancer and anaplastic thyroid cancer, respectively, displaying an association with aggressive types of thyroid cancer. TERT promoter mutations are associated with aggressive thyroid tumor characteristics, tumor recurrence and patient mortality as well as BRAF V600E mutation. Coexisting BRAF V600E and TERT promoter mutations have a robust synergistic impact on the aggressiveness of PTC, including a sharply increased tumor recurrence and patient mortality, while either mutation alone has a modest impact. Thus, TERT with promoter mutations represents a prominent new oncogene in thyroid cancer and the mutations are promising new diagnostic and prognostic genetic markers for thyroid cancer, which, in combination with BRAF V600E mutation or other genetic markers (e.g. RAS mutations), are proving to be clinically useful for the management of thyroid cancer. Future studies will specifically define such clinical utilities, elucidate the biological mechanisms and explore the potential as therapeutic targets of TERT promoter mutations in thyroid cancer.


Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3200
Author(s):  
Alessandro Prete ◽  
Antonio Matrone ◽  
Carla Gambale ◽  
Liborio Torregrossa ◽  
Elisa Minaldi ◽  
...  

PDTC and ATC present median overall survival of 6 years and 6 months, respectively. In spite of their rarity, patients with PDTC and ATC represent a significant clinical problem, because of their poor survival and the substantial inefficacy of classical therapies. We reviewed the newest findings about genetic features of PDTC and ATC, from mutations occurring in DNA to alterations in RNA. Therefore, we describe their tumor microenvironments (both immune and not-immune) and the interactions between tumor and neighboring cells. Finally, we recapitulate how this upcoming evidence are changing the treatment of PDTC and ATC.


2021 ◽  
Vol 104 (3) ◽  
pp. 003685042110180
Author(s):  
Xiao Lin ◽  
Meng Zhou ◽  
Zehong Xu ◽  
Yusheng Chen ◽  
Fan Lin

In this study, we aimed to screen out genes associated with a high risk of postoperative recurrence of lung adenocarcinoma and investigate the possible mechanisms of the involvement of these genes in the recurrence of lung adenocarcinoma. We identify Hub genes and verify the expression levels and prognostic roles of these genes. Datasets of GSE40791, GSE31210, and GSE30219 were obtained from the Gene Expression Omnibus database. Enrichment analysis of gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed for the screened candidate genes using the DAVID database. Then, we performed protein–protein interaction (PPI) network analysis through the database STRING. Hub genes were screened out using Cytoscape software, and their expression levels were determined by the GEPIA database. Finally, we assessed the relationships of Hub genes expression levels and the time of survival. Forty-five candidate genes related to a high-risk of lung adenocarcinoma recurrence were screened out. Gene ontology analysis showed that these genes were enriched in the mitotic spindle assembly checkpoint, mitotic sister chromosome segregation, G2/M-phase transition of the mitotic cell cycle, and ATP binding, etc. KEGG analysis showed that these genes were involved predominantly in the cell cycle, p53 signaling pathway, and oocyte meiosis. We screened out the top ten Hub genes related to high expression of lung adenocarcinoma from the PPI network. The high expression levels of eight genes (TOP2A, HMMR, MELK, MAD2L1, BUB1B, BUB1, RRM2, and CCNA2) were related to short recurrence-free survival and they can be used as biomarkers for high risk of lung adenocarcinoma recurrence. This study screened out eight genes associated with a high risk of lung adenocarcinoma recurrence, which might provide novel insights into researching the recurrence mechanisms of lung adenocarcinoma as well as into the selection of targets in the treatment of the disease.


2019 ◽  
Vol 10 (6) ◽  
pp. 1469-1478
Author(s):  
Hongxia Shang ◽  
Shengnan Wang ◽  
Jinming Yao ◽  
Congcong Guo ◽  
Jianjun Dong ◽  
...  

2006 ◽  
Vol 13 (2) ◽  
pp. 119-128 ◽  
Author(s):  
Kepal N. Patel ◽  
Ashok R. Shaha

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