scholarly journals Identification of Differentially Expressed Kinase and Screening Potential Anticancer Drugs in Papillary Thyroid Carcinoma

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Huairong Zhang ◽  
Bo Gao ◽  
Bingyin Shi
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Signaling Pathway ◽  
Protein Kinases ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Papillary Thyroid

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.

Identification of Differentially Expressed Genes Associated with Papillary Thyroid Carcinoma

2020 ◽  
Vol 23 (6) ◽  
pp. 546-553
Author(s):  
Hongyuan Cui ◽  
Mingwei Zhu ◽  
Junhua Zhang ◽  
Wenqin Li ◽  
Lihui Zou ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
Mrna Level ◽  
Thyroid Tissue ◽  
Differentially Expressed ◽  
Thyroid Tumors ◽  
Papillary Thyroid

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.

scholarly journals A Novel Metastasis-related Genes Based Signature for Predicting the Progression-free Interval of Patients With Papillary Thyroid Carcinoma

2022 ◽  
Author(s):  
Rui Liu ◽  
Zhen Cao ◽  
Meng-wei Wu ◽  
Xiao-bin Li ◽  
Hong-wei Yuan ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Bioinformatic Analysis ◽  
Functional Enrichment ◽  
Clinical Parameters ◽  
Papillary Thyroid ◽  
Free Interval

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.

scholarly journals Comprehensive Analysis of Differentially Expressed Profiles of mRNA, lncRNA, and circRNA in the Uterus of Seasonal Reproduction Sheep

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 301 ◽  
Author(s):  
Yongfu La ◽  
Xiaoyun He ◽  
Liping Zhang ◽  
Ran Di ◽  
Xiangyu Wang ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Seasonal Reproduction ◽  
Hormone Synthesis ◽  
Long Photoperiod

Photoperiod is one of the important factors leading to seasonal reproduction of sheep. However, the molecular mechanisms underlying the photoperiod regulation of seasonal reproduction remain poorly understood. In this study, we compared the expression profiles of mRNAs, lncRNAs, and circRNAs in uterine tissues from Sunite sheep during three different photoperiods, namely, the short photoperiod (SP), short transfer to long photoperiod (SLP), and long photoperiod (LP). The results showed that 298, 403, and 378 differentially expressed (DE) mRNAs, 171, 491, and 499 DE lncRNAs, and 124, 270, and 400 DE circRNAs were identified between SP and LP, between SP and SLP, and between LP and SLP, respectively. Furthermore, functional enrichment analysis showed that the differentially expressed RNAs were mainly involved in the GnRH signaling pathway, thyroid hormone synthesis, and thyroid hormone signaling pathway. In addition, co-expression networks of lncRNA–mRNA were constructed based on the correlation analysis between the differentially expressed RNAs. Our study provides new insights into the expression changes of RNAs in different photoperiods, which might contribute to understanding the molecular mechanisms of seasonal reproduction in sheep.

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 ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Differentially Expressed Genes ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Papillary Thyroid ◽  
Topological Properties ◽  
Network Analyses ◽  
Genetic Mechanisms

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.

scholarly journals Integrated bioinformatics analysis and screening of hub genes in papillary thyroid carcinoma

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0251962
Author(s):  
Rong Fan ◽  
Lijin Dong ◽  
Ping Li ◽  
Xiaoming Wang ◽  
Xuewei Chen
Keyword(s):  
Gene Ontology ◽  
Survival Analysis ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Differentially Expressed Genes ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Papillary Thyroid ◽  
Hub Genes ◽  
Online Software

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.

scholarly journals lncRNA-miRNA-mRNA ceRNA Network in Thyroid Carcinoma from The Cancer Genome Atlas

2020 ◽  
Author(s):  
Guoheng Mo ◽  
Qunguang Jiang ◽  
Zixuan Wang ◽  
Zhaoting Zheng ◽  
XiaoSi Chen
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Molecular Mechanisms ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Papillary Thyroid ◽  
Cerna Network ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Abstract Increasing evidence indicates that the competitive endogenous RNA (ceRNA) hypothesis, that is, long non-coding RNA (LncRNA) can competitively bind microRNA (miRNA) through miRNA response elements to affect the expression of target RNA, and dysregulation of LncRNA expression plays a key role in tumor progression. The papillary thyroid carcinoma that we studied is the most significant pathological type of thyroid cancer, but its ceRNA network has not been extensively evaluated. We analyzed level-3 data from RNA-Seq of 58 para-carcinoma tissues and 501 patients with primary papillary thyroid carcinoma (PTC) using the DEseq software package and downloaded clinical information from The Cancer Genome Atlas (TCGA) to find potential biomarkers or therapeutic targets. As a result, 149 differential miRNAs were selected, including 117 up -regulated, 32 down-regulated, and 3099 differential mRNAs, including 1976 up-regulated, 1123 down-regulated, and 434 differential lncRNAs, including 331 up-regulated and 103 down-regulated (Fold Change > 2, P < 0.05). The interactions between these differentially expressed RNA groups constitute the ceRNA network of PTC. Moreover, we used the microde database to predict the miRNAs that may be acted by the above screened differential lncRNAs and intersected with the selected miRNAs, and further predicted the target genes of the intersecting miRNAs by TargetScan, miRTarBase and miRDB, and intersected with the selected mRNAs. From the constructed ceRNA network we can see that Linc00460 may cause the invasion and metastasis of PTC by competitively inhibiting hsa-mir-150 and upregulating the expression of its downstream target gene EREG. Our study identified a series of lncRNAs associated with PTC progression and prognosis, and this complex ceRNA interaction network provides guidance for better understanding of the molecular mechanisms of PTC and can be used as an effective diagnostic tool for PTC invasion, metastasis and prognosis. Kaplan-Meier analysis of the differentially expressed RNAs associated with PTC pathogenesis confirmed that the lncRNAs AC097717.1, C20orf203, EMX2OS were potentially associated with the prognosis of PTC (P<0.05).

BRAFV600E MUTATION IN PAPILLARY THYROID CARCINOMA. CLINICAL AND METHODOLOGICAL ASPECTS

2019 ◽  
Vol 65 (1) ◽  
pp. 16-26
Author(s):  
Pavel Rumyantsev ◽  
Petr Nikiforovich ◽  
Andrey Poloznikov ◽  
Andrey Abrosimov ◽  
Vladimir Saenko ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Kinase Inhibitors ◽  
Anaplastic Carcinoma ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Brafv600e Mutation ◽  
Wide Range ◽  
Methodological Aspects

Mutation BRAFV600E is highly specific for papillary thyroid carcinoma. It’s detected in 40-70% of all papillary thyroid carcinoma cases. Moreover this mutation is noticed in anaplastic carcinoma in 40-50%.This fact gives a chance to select patients and provide targeted therapy with multi-kinase inhibitors in cases of unresectable anaplastic carcinoma. The influence of BRAF V600E mutation for response to radioactive iodine therapy requires more evidence-based research. Existing methods for determining the BRAFV600E mutation have different accuracy, availability and cost. Other methodological aspects are also associated with the sample preparation of biological material, the quality of reagents, and the cross-validation of research results. In this review, on the basis of our own experience and literature data, the indications for determining the mutation of the BRAFV600E gene in clinical practice are refined, and a comprehensive comparative analysis of modern research methods has been conducted. This review is focused on a wide range of specialists of different types: oncologists, endocrinologists, radiologists, pathologists, and biologists.

Systems Biology Approaches Reveal a Multi-stress Responsive WRKY Transcription Factor and Stress Associated Gene Co-expression Networks in Chickpea

2019 ◽  
Vol 14 (7) ◽  
pp. 591-601 ◽  
Author(s):  
Aravind K. Konda ◽  
Parasappa R. Sabale ◽  
Khela R. Soren ◽  
Shanmugavadivel P. Subramaniam ◽  
Pallavi Singh ◽  
...  
Keyword(s):  
Expression Pattern ◽  
Gene Networks ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Wrky Transcription Factor ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Callose Deposition ◽  
Significant Probability

Background: Chickpea is a nutritional rich premier pulse crop but its production encounters setbacks due to various stresses and understanding of molecular mechanisms can be ascribed foremost importance. Objective: The investigation was carried out to identify the differentially expressed WRKY TFs in chickpea in response to herbicide stress and decipher their interacting partners. Methods: For this purpose, transcriptome wide identification of WRKY TFs in chickpea was done. Behavior of the differentially expressed TFs was compared between other stress conditions. Orthology based cofunctional gene networks were derived from Arabidopsis. Gene ontology and functional enrichment analysis was performed using Blast2GO and STRING software. Gene Coexpression Network (GCN) was constructed in chickpea using publicly available transcriptome data. Expression pattern of the identified gene network was studied in chickpea-Fusarium interactions. Results: A unique WRKY TF (Ca_08086) was found to be significantly (q value = 0.02) upregulated not only under herbicide stress but also in other stresses. Co-functional network of 14 genes, namely Ca_08086, Ca_19657, Ca_01317, Ca_20172, Ca_12226, Ca_15326, Ca_04218, Ca_07256, Ca_14620, Ca_12474, Ca_11595, Ca_15291, Ca_11762 and Ca_03543 were identified. GCN revealed 95 hub genes based on the significant probability scores. Functional annotation indicated role in callose deposition and response to chitin. Interestingly, contrasting expression pattern of the 14 network genes was observed in wilt resistant and susceptible chickpea genotypes, infected with Fusarium. Conclusion: This is the first report of identification of a multi-stress responsive WRKY TF and its associated GCN in chickpea.

Identification of key mRNAs, miRNAs, and mRNA-miRNA network involved in papillary thyroid carcinoma

2020 ◽  
Vol 15 ◽  
Author(s):  
Wei Han ◽  
Dongchen Lu ◽  
Chonggao Wang ◽  
Mengdi Cui ◽  
Kai Lu
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Differential Expression Analysis ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Integrated Analysis ◽  
Papillary Thyroid ◽  
Gene Set Enrichment ◽  
Mirna Expression Data

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.

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