scholarly journals Network Analyses of Integrated Differentially Expressed Genes in Papillary Thyroid Carcinoma to Identify Characteristic Genes

Genes ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 45 ◽  
Author(s):  
Junliang Shang ◽  
Qian Ding ◽  
Shasha Yuan ◽  
Jin-Xing Liu ◽  
Feng Li ◽  
...  

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Identifying characteristic genes of PTC are of great importance to reveal its potential genetic mechanisms. In this paper, we proposed a framework, as well as a measure named Normalized Centrality Measure (NCM), to identify characteristic genes of PTC. The framework consisted of four steps. First, both up-regulated genes and down-regulated genes, collectively called differentially expressed genes (DEGs), were screened and integrated together from four datasets, that is, GSE3467, GSE3678, GSE33630, and GSE58545; second, an interaction network of DEGs was constructed, where each node represented a gene and each edge represented an interaction between linking nodes; third, both traditional measures and the NCM measure were used to analyze the topological properties of each node in the network. Compared with traditional measures, more genes related to PTC were identified by the NCM measure; fourth, by mining the high-density subgraphs of this network and performing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, several meaningful results were captured, most of which were demonstrated to be associated with PTC. The experimental results proved that this network framework and the NCM measure are useful for identifying more characteristic genes of PTC.

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0251962
Author(s):  
Rong Fan ◽  
Lijin Dong ◽  
Ping Li ◽  
Xiaoming Wang ◽  
Xuewei Chen

Background With the increasing incidence of papillary thyroid carcinoma (PTC), PTC continues to garner attention worldwide; however its pathogenesis remains to be elucidated. The purpose of this study was to explore key biomarkers and potential new therapeutic targets for, PTC. Methods GEO2R and Venn online software were used for screening of differentially expressed genes. Hub genes were screened via STRING and Cytoscape, followed by Gene Ontology and KEGG enrichment analysis. Finally, survival analysis and expression validation were performed using the UALCAN online software and immunohistochemistry. Results We identified 334 consistently differentially expressed genes (DEGs) comprising 136 upregulated and 198 downregulated genes. Gene Ontology enrichment analysis results suggested that the DEGs were mainly enriched in cancer-related pathways and functions. PPI network visualization was performed and 17 upregulated and 13 downregulated DEGs were selected. Finally, the expression verification and overall survival analysis conducted using the Gene Expression Profiling Interactive Analysis Tool (GEPIA) and UALCAN showed that LPAR5, TFPI, and ENTPD1 were associated with the development of PTC and the prognosis of PTC patients, and the expression of LPAR5, TFPI and ENTPD1 was verified using a tissue chip. Conclusions In summary, the hub genes and pathways identified in the present study not only provide information for the development of new biomarkers for PTC but will also be useful for elucidation of the pathogenesis of PTC.


2020 ◽  
Vol 23 (6) ◽  
pp. 546-553
Author(s):  
Hongyuan Cui ◽  
Mingwei Zhu ◽  
Junhua Zhang ◽  
Wenqin Li ◽  
Lihui Zou ◽  
...  

Objective: Next-generation sequencing (NGS) was performed to identify genes that were differentially expressed between normal thyroid tissue and papillary thyroid carcinoma (PTC). Materials & Methods: Six candidate genes were selected and further confirmed with quantitative real-time polymerase chain reaction (qRT-PCR), and immunohistochemistry in samples from 24 fresh thyroid tumors and adjacent normal tissues. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was used to investigate signal transduction pathways of the differentially expressed genes. Results: In total, 1690 genes were differentially expressed between samples from patients with PTC and the adjacent normal tissue. Among these, SFRP4, ZNF90, and DCN were the top three upregulated genes, whereas KIRREL3, TRIM36, and GABBR2 were downregulated with the smallest p values. Several pathways were associated with the differentially expressed genes and involved in cellular proliferation, cell migration, and endocrine system tumor progression, which may contribute to the pathogenesis of PTC. Upregulation of SFRP4, ZNF90, and DCN at the mRNA level was further validated with RT-PCR, and DCN expression was further confirmed with immunostaining of PTC samples. Conclusion: These results provide new insights into the molecular mechanisms of PTC. Identification of differentially expressed genes should not only improve the tumor signature for thyroid tumors as a diagnostic biomarker but also reveal potential targets for thyroid tumor treatment.


2020 ◽  
Vol 15 ◽  
Author(s):  
Wei Han ◽  
Dongchen Lu ◽  
Chonggao Wang ◽  
Mengdi Cui ◽  
Kai Lu

Background: In the past decades, the incidence of thyroid cancer (TC) has been gradually increasing, owing to the widespread use of ultrasound scanning devices. However, the key mRNAs, miRNAs, and mRNA-miRNA network in papillary thyroid carcinoma (PTC) has not been fully understood. Material and Methods: In this study, multiple bioinformatics methods were employed, including differential expression analysis, gene set enrichment analysis, and miRNA-mRNA interaction network construction. Results: First, we investigated the key miRNAs that regulated significantly more differentially expressed genes based on GSEA method. Second, we searched for the key miRNAs based on the mRNA-miRNA interaction subnetwork involved in PTC. We identified hsa-mir-1275, hsa-mir-1291, hsa-mir-206 and hsa-mir-375 as the key miRNAs involved in PTC pathogenesis. Conclusion: The integrated analysis of the gene and miRNA expression data not only identified key mRNAs, miRNAs, and mRNA-miRNA network involved in papillary thyroid carcinoma, but also improved our understanding of the pathogenesis of PTC.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Huairong Zhang ◽  
Bo Gao ◽  
Bingyin Shi

Aim. We aim to identify protein kinases involved in the pathophysiology of papillary thyroid carcinoma (PTC) in order to provide potential therapeutic targets for kinase inhibitors and unfold possible molecular mechanisms.Materials and Methods. The gene expression profile of GSE27155 was analyzed to identify differentially expressed genes and mapped onto human protein kinases database. Correlation of kinases with PTC was addressed by systematic literature search, GO and KEGG pathway analysis.Results. The functional enrichment analysis indicated that “mitogen-activated protein kinases pathway” expression was extremely enriched, followed by “neurotrophin signaling pathway,” “focal adhesion,” and “GnRH signaling pathway.” MAPK, SRC, PDGFRa, ErbB, and EGFR were significantly regulated to correct these pathways. Kinases investigated by the literature on carcinoma were considered to be potential novel molecular therapeutic target in PTC and application of corresponding kinase inhibitors could be possible therapeutic tool.Conclusion. SRC, MAPK, and EGFR were the most important differentially expressed kinases in PTC. Combined inhibitors may have high efficacy in PTC treatment by targeting these kinases.


Author(s):  
Zheng Zhang ◽  
Shuangshuang Zhao ◽  
Keke Wang ◽  
Mengyuan Shang ◽  
Zheming Chen ◽  
...  

Integrated analysis of accumulated data is an effective way to obtain reliable potential diagnostic molecular of cervical lymph node metastases (LNM) in papillary thyroid carcinoma (PTC). The benefits of prophylactic lymph node dissection (PLND) for these clinically node-negative (cN0) patients remained considerable controversies. Hence, elucidation of the mechanisms of LNM and exploration of potential biomarkers and prognostic indicators are essential for accurate diagnosis of LNM in PTC patients. Up to date, advanced microarray and bioinformatics analysis have advanced an understanding of the molecular mechanisms of disease occurrence and development, which are necessary to explore genetic changes and identify potential diagnostic biomarkers. In present study, we performed a comprehensive analysis of the differential expression, biological functions, and interactions of LNM-related genes. Two publicly available microarray datasets GSE60542 and GSE129562 were available from Gene Expression Omnibus (GEO) database. Differentially expressed genes between clinically node-positive (cN1) and cN0 PTC samples were screened by an integrated analysis of multiple gene expression profile after gene reannotation and batch normalization. Our results identified 48 differentially expressed genes (DEGs) genetically associated with LNM in PTC patients. Gene ontology (GO) analyses revealed the changes in the modules were mostly enriched in the regulation of MHC class II receptor activity, the immune receptor activity, and the peptide antigen binding. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of DEGs displayed that the intestinal immune network for IgA production, staphylococcus aureus infection, and cell adhesion molecules (CAMs). To screen core genes related to LNM of PTC from the protein-protein interaction network, top 10 hub genes were identified with highest scores. Our results help us understand the exact mechanisms underlying the metastasis of cervical LNM in PTC tissues and pave an avenue for the progress of precise medicine for individual patients.


2020 ◽  
Vol 40 (8) ◽  
Author(s):  
Gang Xue ◽  
Xu Lin ◽  
Jing-Fang Wu ◽  
Da Pei ◽  
Dong-Mei Wang ◽  
...  

Abstract Background: Papillary thyroid carcinoma (PTC) is one of the fastest-growing malignant tumor types of thyroid cancer. Therefore, identifying the interaction of genes in PTC is crucial for elucidating its pathogenesis and finding more specific molecular biomarkers. Methods: Four pairs of PTC tissues and adjacent tissues were sequenced using RNA-Seq, and 3745 differentially expressed genes were screened (P<0.05, |logFC|>1). The enrichment analysis indicated that the vast majority of differentially expressed genes (DEGs) may play a positive role in the development of cancer. Then, the significant modules were analyzed using Cytoscape software in the protein–protein interaction network. Survival analysis, TNM analysis, and immune infiltration analysis of key genes were analyzed. And the expression of ADORA1, APOE, and LPAR5 genes were verified by qPCR in PTC compared with matching adjacent tissues. Results: Twenty-five genes were identified as hub genes with nodes greater than 10. The expression of 25 genes were verified by the GEPIA database, and the overall survival and disease-free survival analyses were conducted with Kaplan–Meier plotter. We found only three genes were confirmed with our validation and were statistically significant in PTC, namely ADORA1, APOE, and LPAR5. Further analysis found that the mRNA levels and methylation degree of these three genes were significantly correlated with the TNM staging of PTC. And these three genes were related to PTC immune infiltration. Verification of the expression of these three genes by RT-qPCR and Western blot further confirmed the reliability of our results. Conclusion: Our study identified three genes that may play key regulatory roles in the development, metastasis, and immune infiltration of papillary thyroid carcinoma.


2020 ◽  
Vol 9 (2) ◽  
pp. LMT30
Author(s):  
Chuanli Ren ◽  
Weixiu Sun ◽  
Xu Lian ◽  
Chongxu Han

Aim: To screen and identify key genes related to the development of smoking-induced lung adenocarcinoma (LUAD). Materials & methods: We obtained data from the GEO chip dataset GSE31210. The differentially expressed genes were screened by GEO2R. The protein interaction network of differentially expressed genes was constructed by STRING and Cytoscape. Finally, core genes were screened. The overall survival time of patients with the core genes was analyzed by Kaplan–Meier method. Gene ontology and Kyoto encyclopedia of genes and genomes bioaccumulation was calculated by DAVID. Results: Functional enrichment analysis indicated that nine key genes were actively involved in the biological process of smoking-related LUAD. Conclusion: 23 core genes and nine key genes among them were correlated with adverse prognosis of LUAD induced by smoking.


2022 ◽  
Author(s):  
Rui Liu ◽  
Zhen Cao ◽  
Meng-wei Wu ◽  
Xiao-bin Li ◽  
Hong-wei Yuan ◽  
...  

Abstract Background: We aimed to build a novel model with metastasis-related genes (MTGs) signature and relevant clinical parameters for predicting progression-free interval (PFI) after surgery for papillary thyroid carcinoma (PTC).Methods: We performed a bioinformatic analysis of integrated PTC datasets with the MTGs to identify differentially expressed MTGs (DE-MTGs). Then we generated PFI-related DE-MTGs and established a novel MTGs based signature. After that, we validated the signature on multiple datasets and PTC cell lines. Further, we carried out uni- and multivariate analysis to identify independent prognostic characters. Finally, we established a signature and clinical parameters-based nomogram for predicting the PFI of PTC. Results: We identified 155 DE-MTGs related to PFI in PTC. The functional enrichment analysis showed that the DE-MTGs were associated with an essential oncogenic process. Consequently, we found a novel 10-gene signature and could distinguish patients with poorer prognoses and predicted PFI accurately. The novel signature had a C-index of 0.76 and the relevant nomogram had a C-index of 0.80. Also, it was closely related to pivotal clinical characters of datasets and invasiveness of cell lines. And the signature was confirmed a significant independent prognostic factor in PTC. Finally, we built a nomogram by including the signature and relevant clinical factors. Validation analysis showed that the nomogram's efficacy was satisfying in predicting PTC’s PFI. Conclusions: The MTG signature and nomogram were closely associated with PTC prognosis and may help clinicians improve the individualized prediction of PFI, especially for high-risk patients after surgery.


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