scholarly journals Comprehensive Identification of Potential Crucial Genes and miRNA-mRNA Regulatory Networks in Papillary Thyroid Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-25
Author(s):  
Ben-yu Nan ◽  
Guo-Feng Xiong ◽  
Zi-Rui Zhao ◽  
Xi Gu ◽  
Xin-Sheng Huang
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Regulatory Networks ◽  
Thyroid Nodules ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Papillary Thyroid ◽  
Ppi Network ◽  
Hub Genes ◽  
Age Related

Background. Thyroid cancer is the most common endocrine malignancy, with a recent global increase of 20% in age-related incidence. Ultrasonography and ultrasonography-guided fine-needle aspiration biopsy (FNAB) are the most widely used diagnostic tests for thyroid nodules; however, it is estimated that up to 25% of thyroid biopsies are cytologically inconclusive. Molecular markers can help guide patient-oriented and targeted treatment of thyroid nodules and thyroid cancer. Methods. Datasets related to papillary thyroid cancer (PTC) or thyroid carcinoma (GSE129562, GSE3678, GSE54958, GSE138042, and GSE124653) were downloaded from the GEO database and analysed using the Limma package of R software. For functional enrichment analysis, the Kyoto Encyclopedia of Genes and Genomes pathway analysis and Gene Ontology were applied to differentially expressed genes (DEGs) using the Metascape website. A protein-protein interaction (PPI) network was built from the STRING database. Gene expression, protein expression, immunohistochemistry, and potential functional gene survival were analysed using the GEPIA website, the Human Protein Atlas website, and the UALCAN website. Potential target miRNAs were predicted using the miRDB and Starbase datasets. Results. We found 219 upregulated and 310 downregulated DEGs, with a cut-off of p < 0.01 and ∣ log   FC ∣ > 1.5 . The DEGs in papillary thyroid cancer were mainly enriched in extracellular structural organisation. At the intersection of the PPI network and Metascape MCODEs, the hub genes in common were identified as FN1, APOE, CLU, and SDC2. In the targeted regulation network of miRNA-mRNA, the hsa-miR-424-5p was found to synchronously modulate two hub genes. Survival analysis showed that patients with high expression of CLU and APOE had better prognosis. Conclusions. CLU and APOE are involved in the molecular mechanism of papillary thyroid cancer. The hsa-miR-424-5p might have the potential to reverse the processes of papillary thyroid cancer by modulating the hub genes. These are potential targets for the treatment of patients with papillary thyroid cancer.

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

2020 ◽  
Author(s):  
Rong Fan ◽  
Lijin Dong ◽  
Ping Li ◽  
Xiaoming Wang ◽  
Xuewei Chen
Keyword(s):  
Gene Ontology ◽  
Survival Analysis ◽  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Enrichment Analysis ◽  
Analysis Tool ◽  
Papillary Thyroid ◽  
Hub Genes ◽  
New Biomarkers ◽  
Online Software

Abstract Background With the increasing incidence, papillary thyroid cancer (PTC) is receiving more and more attention, but the pathogenesis of which is still not completely elucidated. The purpose of this study was to explore key biomarkers and new therapeutic targets in PTC. Methods GEO2R and Venn online software were used for differential gene screening analysis. Hub genes were screened via STRING and Cytoscape, following Gene Ontology and KEGG enrichment analysis. Finally, survival analysis and expression validation were performed via UALCAN online software and immunohistochemistry. Results We screened 334 consistently differentially expressed genes (DEGs), composed of 136 upregulated genes and 198 downregulated genes. Gene ontology enrichment analysis suggested that DEGs mainly enriched in the cancer-related pathways and functions. PPI network visualization was performed to select 17 upregulated and 13 downregulated DEGs. Finally, the expression verification and overall survival analysis conducted in the Gene Expression Profiling Interactive Analysis Tool (GEPIA) and UALCAN showed that LPAR5, TFPI and ENTPD1 were related to the development of PTC and the prognosis of PTC patients, and the expression of LPAR5 was verified by tissue chip. Conclusions In summary, the hub genes and pathways identified in the present study not only provided new biomarkers for PTC, but also will be useful for elucidating the pathogenesis of PTC.

scholarly journals Integrated Analysis of lncRNAs, mRNAs, and TFs to Identify Regulatory Networks Underlying MAP Infection in Cattle

2021 ◽  
Vol 12 ◽  
Author(s):  
Maryam Heidari ◽  
Abbas Pakdel ◽  
Mohammad Reza Bakhtiarizadeh ◽  
Fariba Dehghanian
Keyword(s):  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Johne's Disease ◽  
Johne’S Disease ◽  
Functional Enrichment ◽  
Integrated Analysis ◽  
Complex Nature ◽  
Hub Genes ◽  
Cis And Trans

Johne’s disease is a chronic infection of ruminants that burdens dairy herds with a significant economic loss. The pathogenesis of the disease has not been revealed clearly due to its complex nature. In order to achieve deeper biological insights into molecular mechanisms involved in MAP infection resulting in Johne’s disease, a system biology approach was used. As far as is known, this is the first study that considers lncRNAs, TFs, and mRNAs, simultaneously, to construct an integrated gene regulatory network involved in MAP infection. Weighted gene coexpression network analysis (WGCNA) and functional enrichment analysis were conducted to explore coexpression modules from which nonpreserved modules had altered connectivity patterns. After identification of hub and hub-hub genes as well as TFs and lncRNAs in the nonpreserved modules, integrated networks of lncRNA-mRNA-TF were constructed, and cis and trans targets of lncRNAs were identified. Both cis and trans targets of lncRNAs were found in eight nonpreserved modules. Twenty-one of 47 nonpreserved modules showed significant biological processes related to the immune system and MAP infection. Some of the MAP infection’s related pathways in the most important nonpreserved modules comprise “positive regulation of cytokine-mediated signaling pathway,” “negative regulation of leukocyte migration,” “T-cell differentiation,” “neutrophil activation,” and “defense response.” Furthermore, several genes were identified in these modules, including SLC11A1, MAPK8IP1, HMGCR, IFNGR1, CMPK2, CORO1A, IRF1, LDLR, BOLA-DMB, and BOLA-DMA, which are potentially associated with MAP pathogenesis. This study not only enhanced our knowledge of molecular mechanisms behind MAP infection but also highlighted several promising hub and hub-hub genes involved in macrophage-pathogen interaction.

Serum osteopontin can improve papillary thyroid cancer risk assessment of Bethesda III thyroid nodules: a preliminary study

2021 ◽  
Author(s):  
Taha Ulutan Kars ◽  
Mustafa Kulaksizoglu ◽  
İbrahim Kılınç
Keyword(s):  
Thyroid Cancer ◽  
Cancer Risk ◽  
Papillary Thyroid Cancer ◽  
Thyroid Nodules ◽  
Cancer Risk Assessment ◽  
Papillary Thyroid ◽  
Operating Characteristics ◽  
Discriminative Performance ◽  
Thyroid Cancer Risk ◽  
Preliminary Study

Objective: Thyroid cancer can be detected in 5–10% of patients with thyroid nodules. Management may be a challenge if fine-needle aspiration biopsy yields Bethesda III findings. Most of these cases undergo surgery and are ultimately found benign. Our aim was to evaluate whether serum osteopontin can accurately estimate thyroid cancer risk in cases with cytologically Bethesda III thyroid nodules and, thereby, decrease the number of unnecessary surgical interventions. Design and Methods: We obtained blood samples of cases with repeated cytologically Bethesda III thyroid nodules before surgery, and followed up the pathology results after thyroidectomy. We evaluated serum osteopontin from 36 patients with papillary thyroid cancer and compared them with 40 benign cases. Results: Serum osteopontin levels in patients with papillary thyroid cancer are significantly higher than in benign cases (mean serum osteopontin: 10.48 ± 3.51 ng/mL vs 6.14 ± 2.29 ng/mL, p<0.001). The area under the receiver operating characteristics curve was 0.851, suggesting that serum osteopontin could have considerable discriminative performance. Conclusions: In our preliminary study, high serum osteopontin levels can predict the risk of papillary thyroid cancer in thyroid nodules with Bethesda III cytology. Further studies are necessary to confirm these findings.

scholarly journals BCL2 and hsa-miR-181a-5p are potential biomarkers associated with papillary thyroid cancer based on bioinformatics analysis

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Cong Zhang ◽  
Chunrui Bo ◽  
Lunhua Guo ◽  
Pingyang Yu ◽  
Susheng Miao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thyroid Cancer ◽  
Gene Regulatory Network ◽  
Papillary Thyroid Cancer ◽  
Regulatory Network ◽  
Mirna Gene ◽  
Cancer Type ◽  
Papillary Thyroid ◽  
Ppi Network ◽  
Gene Regulatory

Abstract Background The morbidity of thyroid carcinoma has been rising worldwide and increasing faster than any other cancer type. The most common subtype with the best prognosis is papillary thyroid cancer (PTC); however, the exact molecular pathogenesis of PTC is still not completely understood. Methods In the current study, 3 gene expression datasets (GSE3678, GSE3467, and GSE33630) and 2 miRNA expression datasets (GSE113629 and GSE73182) of PTC were selected from the Gene Expression Omnibus (GEO) database and were further used to identify differentially expressed genes (DEGs) and deregulated miRNAs between normal thyroid tissue samples and PTC samples. Then, Gene Ontology (GO) and pathway enrichment analyses were conducted, and a protein-protein interaction (PPI) network was constructed to explore the potential mechanism of PTC carcinogenesis. The hub gene detection was performed using the CentiScaPe v2.0 plugin, and significant modules were discovered using the MCODE plugin for Cytoscape. In addition, a miRNA-gene regulatory network in PTC was constructed using common deregulated miRNAs and DEGs. Results A total of 263 common DEGs and 12 common deregulated miRNAs were identified. Then, 6 significant KEGG pathways (P < 0.05) and 82 significant GO terms were found to be enriched, indicating that PTC was closely related to amino acid metabolism, development, immune system, and endocrine system. In addition, by constructing a PPI network and miRNA-gene regulatory network, we found that hsa-miR-181a-5p regulated the most DEGs, while BCL2 was targeted by the most miRNAs. Conclusions The results of this study suggested that hsa-miR-181a-5p and BCL2 and their regulatory networks may play important roles in the pathogenesis of PTC.

scholarly journals Xiaoyu Xiezhuo Drink Protects against Ischemia-Reperfusion Acute Kidney Injury in Aged Mice through Inhibiting the TGF-β1/Smad3 and HIF1 Signaling Pathways

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Qingqing Ye ◽  
Hongbo Chen ◽  
Hongzhen Ma ◽  
Xiaojun Xiang ◽  
Shouci Hu ◽  
...  
Keyword(s):  
Drug Targets ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Ppi Network ◽  
Hub Genes ◽  
Aged Mice ◽  
Tgf Β1

Acute kidney injury (AKI) is responsible for significant mortality among hospitalized patients that is especially troubling aged people. An effective self-made Chinese medicine formula, Xiaoyu Xiezhuo Drink (XXD), displayed therapeutic effects on AKI. However, the compositions and underlying mechanisms of XXD remain to be elucidated. In this study, we used the ultra-high-performance liquid chromatography method coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) to investigate the chemical components in XXD. Then, the absorbable components of XXD were identified based on the five principles and inputted into the SwissTargetPrediction and STITCH databases to identify the drug targets. AKI-related targets were collected from the GenCLiP 3, GeneCards, and DisGeNET databases. The crossover genes of XXD and AKI were identified for functional enrichment analysis. The protein-protein interaction (PPI) network of crossover genes was constructed, followed by the identification of hub genes. Subsequently, the effects and potential mechanisms of XXD on AKI predicted by the network pharmacology and bioinformatics analyses were experimentally validated in ischemia-reperfusion (I/R) injury-induced AKI aged mouse models. A total of 122 components in XXD were obtained; among them, 58 components were found that could be absorbed in the blood. There were 800 potential drug targets predicted from the 58 absorbable components in AKI which shared 36 crossover genes with AKI-related targets. The results of functional enrichment analysis indicated that crossover genes mostly associated with the response to oxidative stress and the HIF1 signaling pathway. In the PPI network analysis, 12 hub genes were identified, including ALB, IL-6, TNF, TP53, VEGFA, PTGS2, TLR4, NOS3, EGFR, PPARG, HIF1A, and HMOX1. In AKI aged mice, XXD prominently alleviated I/R injury-induced renal dysfunction, abnormal renal pathological changes, and cellular senescence, inflammation, and oxidative damage with a reduction in the expression level of the inflammatory mediator, α-SMA, collagen-1, F4/80, TP53, VEGFA, PTGS2, TLR4, NOS3, EGFR, PPARG, HIF1A, ICAM-1, TGF-β1, Smad3, and p-Smad3 and an increase of nephridial tissue p-H3, Ki67, HMOX1, MMP-9, and Smad7 levels. In summary, our findings suggest that XXD has renoprotective effects against AKI in aged mice via inhibiting the TGF-β1/Smad3 and HIF1 signaling pathways.

scholarly journals Using Weighted Gene Co-Expression Network Analysis to Identify Key Genes Related to the Onset of Preeclampsia

2020 ◽  
Author(s):  
Xinyang Shen ◽  
Zhijian Wang ◽  
Zhirui Zeng ◽  
Zhenqin Huang ◽  
Xiaowei Huang ◽  
...  
Keyword(s):  
Enrichment Analysis ◽  
Diagnostic Value ◽  
Functional Enrichment ◽  
Immune Response Gene ◽  
Control Group ◽  
Ppi Network ◽  
Hub Genes ◽  
Ontology Term ◽  
Gene Data ◽  
Core Genes

Abstract Background: Preeclampsia is a form of hypertension in pregnancy, which induced by complicated factors. However, the pathogenesis of the disease is unclear. The present study was aimed to discover the critical biomarkers associated with the occurrence and development of preeclampsia. Methods：Gene data profile GSE75010 was downloaded from the Gene Expression Omnibus (GEO) database and used as discovery cohort to establish a WGCNA network determining significant modules which associated with clinical traits. Subsequently, functional enrichment analysis, pathway analysis and protein-protein interaction (PPI) network construction were performed on the core genes in significant modules to identify hub genes. Then, gene data profile GSE25906 was used as verified cohort to determine their diagnostic value of hub genes. The protein expression levels of these hub genes in preeclampsia and control placental tissues were verified using immunohistochemistry method. Finally, GSEA was performed to analyze their enrichment pathways. Results: Total 33 co-expression modules were identified after the establishment of WGCNA, of which 4 gene modules were identified as significant modules because they were related to multiple (>3) clinical traits. Total 75 core genes in significant modules were analyzed, and results showed that they were mainly enriched in adaptive immune response (Gene Ontology term) and platelet activation (Kyoto Encyclopedia of Genes and Genomes term). Finally, a total of 5 genes including TYROBP, PLEK, LCP2, HCK, ITGAM were identified as hub genes which scored high in PPI network and had high diagnostic value. Furthermore, the protein level of these 5 genes in placental tissues of preeclampsia was lower than that of the control group. Moreover, these 5 genes were all enriched in 17 pathways, including autoimmunity pathway. Conclusions：These 5 genes (TYROBP, PLEK, LCP2, HCK, ITGAM) may be closely related to the pathogenesis of preeclampsia, which may also help the diagnosis and therapy of preeclampsia.

scholarly journals Construction of Circular RNA–MicroRNA–Messenger RNA Regulatory Network of Recurrent Implantation Failure to Explore Its Potential Pathogenesis

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiahuan Luo ◽  
Li Zhu ◽  
Ning Zhou ◽  
Yuanyuan Zhang ◽  
Lirong Zhang ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Implantation Failure ◽  
Ppi Network ◽  
Recurrent Implantation Failure ◽  
Hub Genes ◽  
Hub Gene ◽  
Gene Regulatory

Background: Many studies on circular RNAs (circRNAs) have recently been published. However, the function of circRNAs in recurrent implantation failure (RIF) is unknown and remains to be explored. This study aims to determine the regulatory mechanisms of circRNAs in RIF.Methods: Microarray data of RIF circRNA (GSE147442), microRNA (miRNA; GSE71332), and messenger RNA (mRNA; GSE103465) were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed circRNA, miRNA, and mRNA. The circRNA–miRNA–mRNA network was constructed by Cytoscape 3.8.0 software, then the protein–protein interaction (PPI) network was constructed by STRING database, and the hub genes were identified by cytoHubba plug-in. The circRNA–miRNA–hub gene regulatory subnetwork was formed to understand the regulatory axis of hub genes in RIF. Finally, the Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the hub genes were performed by clusterProfiler package of Rstudio software, and Reactome Functional Interaction (FI) plug-in was used for reactome analysis to comprehensively analyze the mechanism of hub genes in RIF.Results: A total of eight upregulated differentially expressed circRNAs (DECs), five downregulated DECs, 56 downregulated differentially expressed miRNAs (DEmiRs), 104 upregulated DEmiRs, 429 upregulated differentially expressed genes (DEGs), and 1,067 downregulated DEGs were identified regarding RIF. The miRNA response elements of 13 DECs were then predicted. Seven overlapping miRNAs were obtained by intersecting the predicted miRNA and DEmiRs. Then, 56 overlapping mRNAs were obtained by intersecting the predicted target mRNAs of seven miRNAs with 1,496 DEGs. The circRNA–miRNA–mRNA network and PPI network were constructed through six circRNAs, seven miRNAs, and 56 mRNAs; and four hub genes (YWHAZ, JAK2, MYH9, and RAP2C) were identified. The circRNA–miRNA–hub gene regulatory subnetwork with nine regulatory axes was formed in RIF. Functional enrichment analysis and reactome analysis showed that these four hub genes were closely related to the biological functions and pathways of RIF.Conclusion: The results of this study provide further understanding of the potential pathogenesis from the perspective of circRNA-related competitive endogenous RNA network in RIF.

scholarly journals Papillary thyroid cancer in an adolescent with a toxic single nodular goiter

2017 ◽  
Vol 63 (2) ◽  
pp. 114-116 ◽  
Author(s):  
Olga S. Rogova ◽  
Goar F. Okminyan ◽  
Lubov N. Samsonova ◽  
Elena V. Kiseleva ◽  
Oleg Yu. Latyshev ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Nodule ◽  
Papillary Thyroid Cancer ◽  
Thyroid Nodules ◽  
Fine Needle Aspiration Biopsy ◽  
Nodular Goiter ◽  
Needle Aspiration ◽  
Papillary Thyroid ◽  
Risk Of Malignancy ◽  
Functional Autonomy

The rate of nodular goiter in children ranges from 0.05 to 5.1%; in this case, the risk of thyroid cancer in childhood amounts to 3―70% of all cases of thyroid pathology. Therefore, the main issue is the differential diagnosis of a nosological variant of a thyroid nodule, which defines the optimal therapeutic tactics for a particular patient. The risk of malignancy is traditionally believed to be low in the case of decompensated functional autonomy of a thyroid nodule; therefore, the need for fine needle aspiration biopsy (FNAB) followed by cytomorphological analysis of the aspirate is avoided in most cases. The presented clinical case demonstrates papillary cancer in an adolescent with a toxic single nodular goiter. A thyroid ultrasound examination revealed a nodular lesion in the boy. An increase in the thyroid size and thyrotoxicosis manifestation occurred 3 years later. A cytomorphological study identified follicular neoplasia; scintigraphy revealed a hot nodule. Surgical treatment was planned. Antithyroid therapy was prescribed to prepare for surgery. After compensation of thyrotoxicosis, hemithyroidectomy was performed. A histological examination diagnosed papillary thyroid cancer, which required repeated thyroidectomy followed by radioiodine I131 ablation. The postoperative period was uneventful; the patient well tolerated suppressive levothyroxine therapy. Therefore, the presence of a toxic single nodular goiter does not exclude thyroid cancer, which defines the need to discuss the indications for FNAB of thyroid nodules in children.

scholarly journals Detection of STRN‐ALK fusion in thyroid nodules with indeterminate cytopathology facilitates papillary thyroid cancer diagnosis

2020 ◽  
Author(s):  
Magdalena Jurkiewicz ◽  
Adela Cimic ◽  
Vundavalli V. Murty ◽  
Jennifer H. Kuo ◽  
Susan Hsiao ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Cancer Diagnosis ◽  
Thyroid Nodules ◽  
Papillary Thyroid
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