scholarly journals Integrated microRNA, gene expression and transcription factors signature in papillary thyroid cancer with lymph node metastasis

2015 ◽  
Author(s):  
Nurul-Syakima Ab Mutalib ◽  
Sri Noraima Othman ◽  
Azliana Mohamad Yusof ◽  
Shahrun Niza Abdullah Suhaimi ◽  
Rohaizak Muhammad ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Papillary Thyroid ◽  
Normal Thyroid ◽  
Node Metastasis ◽  
Differentially Expressed Mirnas

Background: Papillary thyroid carcinoma (PTC) is the commonest thyroid malignancy originating from the follicle cells in the thyroid. Despite a good overall prognosis, certain high-risk cases as in those with lymph node metastasis (LNM) have progressive disease and poorer prognosis. MicroRNAs are a class of non-protein-coding, 19-24 nucleotides single-stranded RNAs which regulate gene expression and these molecules have been shown to play a role in LNM. The integrated analysis of miRNAs and gene expression profiles together with transcription factors (TFs) has been shown to improve the identification of functional miRNA-target gene-TF relationships, providing a more complete view of molecular events underlying metastasis process. Objectives: We reanalyzed The Cancer Genome Atlas (TCGA) datasets on PTC to identify differentially expressed miRNAs/genes in PTC patients with LNM-positive (LNM-P) versus lymph node negative (LNN) PTC patients and to investigate the miRNA-gene-TF regulatory circuit that regulate LNM in PTC. Results: PTC patients with LNM (PTC LNM-P) has significantly shorter disease-free survival rate compared to PTC patients without LNM (PTC LNN) (Log-rank Mantel Cox test, p = 0.0049). We identified 181 significantly differentially expressed miRNAs in PTC LNM-P versus PTC LNN; 110 were upregulated and 71 were downregulated. The five topmost deregulated miRNAs were hsa-miR-146b, hsa-miR-375, hsa-miR-31, hsa-miR-7-2 and hsa-miR-204. In addition, 395 miRNAs were differentially expressed between PTC LNM-P and normal thyroid while 400 miRNAs were differentially expressed between PTC LNN and normal thyroid. We found 4 significant enrichment pathways potentially involved in metastasis to the lymph nodes namely oxidative phosphorylation (OxPhos), cell adhesion molecules (CAMs), leukocyte transendothelial migration and cytokine-cytokine receptor interaction. OxPhos was the most significantly perturbed pathway (p = 4.70E-06) involving downregulation of 90 OxPhos-related genes. Significant interaction of hsa-miR-301b with HLF, HIF and REL/NFkB transcription factors were identified exclusively in PTC LNM-P versus PTC LNN. Conclusion: We found evidence of five miRNAs differentially expressed in PTC LNM-P. Alteration in OxPhos pathway could be the central event in metastasis to the lymph node in PTC. We postulate that hsa-miR-301b might be involved in regulating LNM in PTC via interactions with HLF, HIF and REL/NFkB. To the best of our knowledge, the roles of these TFs have been studied in PTC but the precise role of this miRNA with these TFs in LNM in PTC has not been investigated.

scholarly journals Integrated microRNA, gene expression and transcription factors signature in papillary thyroid cancer with lymph node metastasis

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2119 ◽  
Author(s):  
Nurul-Syakima Ab Mutalib ◽  
Sri Noraima Othman ◽  
Azliana Mohamad Yusof ◽  
Shahrun Niza Abdullah Suhaimi ◽  
Rohaizak Muhammad ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Papillary Thyroid ◽  
Normal Thyroid ◽  
Node Metastasis ◽  
Differentially Expressed Mirnas

Background. Papillary thyroid carcinoma (PTC) is the commonest thyroid malignancy originating from the follicle cells in the thyroid. Despite a good overall prognosis, certain high-risk cases as in those with lymph node metastasis (LNM) have progressive disease and poorer prognosis. MicroRNAs are a class of non-protein-coding, 19-24 nucleotides single-stranded RNAs which regulate gene expression and these molecules have been shown to play a role in LNM. The integrated analysis of miRNAs and gene expression profiles together with transcription factors (TFs) has been shown to improve the identification of functional miRNA-target gene-TF relationships, providing a more complete view of molecular events underlying metastasis process.Objectives. We reanalyzed The Cancer Genome Atlas (TCGA) datasets on PTC to identify differentially expressed miRNAs/genes in PTC patients with LNM-positive (LNM-P) versus lymph node negative (LNN) PTC patients and to investigate the miRNA-gene-TF regulatory circuit that regulate LNM in PTC.Results. PTC patients with LNM (PTC LNM-P) have a significantly shorter disease-free survival rate compared to PTC patients without LNM (PTC LNN) (Log-rank Mantel Cox test,p= 0.0049). We identified 181 significantly differentially expressed miRNAs in PTC LNM-P versus PTC LNN; 110 were upregulated and 71 were downregulated. The five topmost deregulated miRNAs were hsa-miR-146b, hsa-miR-375, hsa-miR-31, hsa-miR-7-2 and hsa-miR-204. In addition, 395 miRNAs were differentially expressed between PTC LNM-P and normal thyroid while 400 miRNAs were differentially expressed between PTC LNN and normal thyroid. We found four significant enrichment pathways potentially involved in metastasis to the lymph nodes, namely oxidative phosphorylation (OxPhos), cell adhesion molecules (CAMs), leukocyte transendothelial migration and cytokine--cytokine receptor interaction. OxPhos was the most significantly perturbed pathway (p= 4.70E−06) involving downregulation of 90 OxPhos-related genes. Significant interaction of hsa-miR-301b with HLF, HIF and REL/NFkB transcription factors were identified exclusively in PTC LNM-P versus PTC LNN.Conclusion. We found evidence of five miRNAs differentially expressed in PTC LNM-P. Alteration in OxPhos pathway could be the central event in metastasis to the lymph node in PTC. We postulate that hsa-miR-301b might be involved in regulating LNM in PTC via interactions with HLF, HIF and REL/NFkB. To the best of our knowledge, the roles of these TFs have been studied in PTC but the precise role of this miRNA with these TFs in LNM in PTC has not been investigated.

scholarly journals Integrated microRNA, gene expression and transcription factors signature in papillary thyroid cancer with lymph node metastasis

2015 ◽  
Author(s):  
Nurul-Syakima Ab Mutalib ◽  
Sri Noraima Othman ◽  
Azliana Mohamad Yusof ◽  
Shahrun Niza Abdullah Suhaimi ◽  
Rohaizak Muhammad ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Papillary Thyroid ◽  
Normal Thyroid ◽  
Node Metastasis ◽  
Differentially Expressed Mirnas

Background: Papillary thyroid carcinoma (PTC) is the commonest thyroid malignancy originating from the follicle cells in the thyroid. Despite a good overall prognosis, certain high-risk cases as in those with lymph node metastasis (LNM) have progressive disease and poorer prognosis. MicroRNAs are a class of non-protein-coding, 19-24 nucleotides single-stranded RNAs which regulate gene expression and these molecules have been shown to play a role in LNM. The integrated analysis of miRNAs and gene expression profiles together with transcription factors (TFs) has been shown to improve the identification of functional miRNA-target gene-TF relationships, providing a more complete view of molecular events underlying metastasis process. Objectives: We reanalyzed The Cancer Genome Atlas (TCGA) datasets on PTC to identify differentially expressed miRNAs/genes in PTC patients with LNM-positive (LNM-P) versus lymph node negative (LNN) PTC patients and to investigate the miRNA-gene-TF regulatory circuit that regulate LNM in PTC. Results: PTC patients with LNM (PTC LNM-P) has significantly shorter disease-free survival rate compared to PTC patients without LNM (PTC LNN) (Log-rank Mantel Cox test, p = 0.0049). We identified 181 significantly differentially expressed miRNAs in PTC LNM-P versus PTC LNN; 110 were upregulated and 71 were downregulated. The five topmost deregulated miRNAs were hsa-miR-146b, hsa-miR-375, hsa-miR-31, hsa-miR-7-2 and hsa-miR-204. In addition, 395 miRNAs were differentially expressed between PTC LNM-P and normal thyroid while 400 miRNAs were differentially expressed between PTC LNN and normal thyroid. We found 4 significant enrichment pathways potentially involved in metastasis to the lymph nodes namely oxidative phosphorylation (OxPhos), cell adhesion molecules (CAMs), leukocyte transendothelial migration and cytokine-cytokine receptor interaction. OxPhos was the most significantly perturbed pathway (p = 4.70E-06) involving downregulation of 90 OxPhos-related genes. Significant interaction of hsa-miR-301b with HLF, HIF and REL/NFkB transcription factors were identified exclusively in PTC LNM-P versus PTC LNN. Conclusion: We found evidence of five miRNAs differentially expressed in PTC LNM-P. Alteration in OxPhos pathway could be the central event in metastasis to the lymph node in PTC. We postulate that hsa-miR-301b might be involved in regulating LNM in PTC via interactions with HLF, HIF and REL/NFkB. To the best of our knowledge, the roles of these TFs have been studied in PTC but the precise role of this miRNA with these TFs in LNM in PTC has not been investigated.

Identification of biomarkers associated with cervical lymph node metastasis in papillary thyroid carcinoma: Evidence from an integrated bioinformatic analysis

2021 ◽  
pp. 1-10
Author(s):  
Zheng Zhang ◽  
Shuangshuang Zhao ◽  
Keke Wang ◽  
Mengyuan Shang ◽  
Zheming Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lymph Node ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Differentially Expressed Genes ◽  
Cervical Lymph Node ◽  
Receptor Activity ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Papillary Thyroid

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.

scholarly journals Radiogenomic Analysis of Papillary Thyroid Carcinoma for Prediction of Cervical Lymph Node Metastasis: A Preliminary Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuyang Tong ◽  
Peixuan Sun ◽  
Juanjuan Yong ◽  
Hongbo Zhang ◽  
Yunxia Huang ◽  
...  
Keyword(s):  
Lymph Node ◽  
Papillary Thyroid Carcinoma ◽  
Lymph Node Metastasis ◽  
Papillary Thyroid ◽  
Hub Genes ◽  
Normal Thyroid ◽  
Protein Protein Interaction ◽  
Node Metastasis ◽  
Gene Modules ◽  
Deviation Ratio

BackgroundPapillary thyroid carcinoma (PTC) is characterized by frequent metastases to cervical lymph nodes (CLNs), and the presence of lymph node metastasis at diagnosis has a significant impact on the surgical approach. Therefore, we established a radiomic signature to predict the CLN status of PTC patients using preoperative thyroid ultrasound, and investigated the association between the radiomic features and underlying molecular characteristics of PTC tumors.MethodsIn total, 270 patients were enrolled in this prospective study, and radiomic features were extracted according to multiple guidelines. A radiomic signature was built with selected features in the training cohort and validated in the validation cohort. The total protein extracted from tumor samples was analyzed with LC/MS and iTRAQ technology. Gene modules acquired by clustering were chosen for their diagnostic significance. A radiogenomic map linking radiomic features to gene modules was constructed with the Spearman correlation matrix. Genes in modules related to metastasis were extracted for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and a protein-protein interaction (PPI) network was built to identify the hub genes in the modules. Finally, the screened hub genes were validated by immunohistochemistry analysis.ResultsThe radiomic signature showed good performance for predicting CLN status in training and validation cohorts, with area under curve of 0.873 and 0.831 respectively. A radiogenomic map was created with nine significant correlations between radiomic features and gene modules, and two of them had higher correlation coefficient. Among these, MEmeganta representing the upregulation of telomere maintenance via telomerase and cell-cell adhesion was correlated with ‘Rectlike’ and ‘deviation ratio of tumor tissue and normal thyroid gland’ which reflect the margin and the internal echogenicity of the tumor, respectively. MEblue capturing cell-cell adhesion and glycolysis was associated with feature ‘minimum calcification area’ which measures the punctate calcification. The hub genes of the two modules were identified by protein-protein interaction network. Immunohistochemistry validated that LAMC1 and THBS1 were differently expressed in metastatic and non-metastatic tissues (p=0.003; p=0.002). And LAMC1 was associated with feature ‘Rectlike’ and ‘deviation ratio of tumor and normal thyroid gland’ (p<0.001; p<0.001); THBS1 was correlated with ‘minimum calcification area’ (p<0.001).ConclusionsThe radiomic signature proposed here has the potential to noninvasively predict the CLN status in PTC patients. Merging imaging phenotypes with genomic data could allow noninvasive identification of the molecular properties of PTC tumors, which might support clinical decision making and personalized management.

scholarly journals In-silico analysis of differentially expressed genes and their regulating microRNA involved in lymph node metastasis in invasive breast carcinoma

2020 ◽  
Author(s):  
Anupama Modi ◽  
Purvi Purohit ◽  
Ashita Gadwal ◽  
Shweta Ukey ◽  
Dipayan Roy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Candidate Genes ◽  
Differentially Expressed Genes ◽  
In Silico ◽  
Nodal Metastasis ◽  
Differentially Expressed ◽  
Hub Genes ◽  
Node Metastasis

AbstractIntroductionAxillary nodal metastasis is related to poor prognosis in breast cancer (BC). The metastatic progression in BC is related to molecular signatures. The currently popular methods to evaluate nodal status may give false negatives or give rise to secondary complications. In this study, key candidate genes in BC lymph node metastasis have been identified from publicly available microarray datasets and their roles in BC have been explored through survival analysis and target prediction.MethodsGene Expression Omnibus datasets have been analyzed for differentially expressed genes (DEGs) in lymph node-positive BC patients compared to nodal-negative and healthy tissues. The functional enrichment analysis was done in database for annotation, visualization and integrated discovery (DAVID). Protein-protein interaction (PPI) network was constructed in Search Tool for the Retrieval of Interacting Genes and proteins (STRING) and visualized on Cytoscape. The candidate hub genes were identified and their expression analyzed for overall survival (OS) in Gene Expression Profiling Interactive Analysis (GEPIA). The target miRNA and transcription factors were analyzed through miRNet.ResultsA total of 102 overlapping DEGs were found. Gene Ontology revealed eleven, seventeen, and three significant terms for cellular component, biological process, and molecular function respectively. Six candidate genes, DSC3, KRT5, KRT6B, KRT17, KRT81, and SERPINB5 were significantly associated with nodal metastasis and OS in BC patients. A total of 83 targeting miRNA were identified through miRNet and hsa-miR-155-5p was found to be the most significant miRNA which was targeting five out of six hub genes.ConclusionIn-silico survival and expression analyses revealed six candidate genes and 83 miRNAs, which may be potential diagnostic markers and therapeutic targets in BC patients and miR-155-5p shows promise as it targeted five important hub genes related to lymph-node metastasis.

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