scholarly journals Identification of aberrantly methylated differentially expressed genes in papillary thyroid carcinoma using integrated bioinformatic analysis

2021 ◽  
Author(s):  
Qingxian Li ◽  
Weiyi Cai ◽  
Jianhong Chen ◽  
Jie Ning
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Regression Analysis ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Integrative Analysis ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Tumor Biomarker ◽  
Papillary Thyroid

Abstract Background: DNA methylation has been reported as one of the most critical epigenetic aberrations during the tumorigenesis and development of papillary thyroid carcinoma (PTC). Although PTC has been explored by gene expression and DNA methylation studies, the regulatory mechanisms of the methylation on the gene expression was poorly clarified.Results: In this study, the comparisons between PTC and NT revealed 4995 methylated probes and 1446 differentially expressed transcripts cross-validated by The Cancer Genome Atlas (TCGA) database. The integrative analysis between DNA methylation and gene expression revealed 123 and 29 genes with hypomethylation/overexpression and hypermethylation/downexpression correlation, respectively. The DNA methylation pattern of seven selected CpGs (A: UNC80-cg04507925; B: TPO-cg09757588; C: LHX8-cg11842415; D: DLG2-cg16986720; E: FOXJ1-cg20373432; F: PALM2-cg21204870; G: IPCEF1-cg24635109, of which the candidate promoter CpG sites were preliminarily identified with the least absolute shrinkage and selection operator (LASSO) regression analysis. Then, the risk prognosis model was constructed by stepwise regression analysis. Furthermore, the receiver operating characteristic (ROC) and nomogram based on the verified independent prognostic factors was established for the prognostic prediction showed that it was able to predict 3-, 5-, and 7-year survival accurately. Kaplan-Meier survival estimate demonstrated that low DLG2 expression and DLG2-cg16986720 hypermethylation were independent biomarkers for OS. From the comprehensive meta-analysis, the combined Standardised Mean Difference (SMD) of DLG2 was 0.94 with 95% CI of (0.46,1.43), indicating that less DLG2 was expressed in the PTC tissue than in the normal tissue (P<0.05). Bisulfite sequencing PCR also showed that DLG2 methylation was higher in tumor group than in normal group. Components of immune microenvironment were analyzed using TIMER, and the correlation between immune cells and DLG2 was found to be distinct across cancer types. Based on Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, DLG2 was implicated in pathways involved in immunity, metabolism, cancer, and infectious diseases. PCT patients with DLG2-cg16986720 hypermethylation showed significantly short survival rates in progression- free survival concomitant with reduced infiltration of myeloid dendritic cells.Conclusions: The current study validated that DLG2 was lowly expressed in PTC. More importantly, DLG2 hypermethylation might function as a latent tumor biomarker in the prognosis prediction for PTC. The results of bioinformatics analyses may present a new method for investigating the pathogenesis of PTC. DNA methylation loss in non-promoter, poor CGI and enhancer-enriched regions was a significant event in PTC. In addition to the promoter region, gene body and 3’UTR methylation have also the potential to influence the gene expression levels (both, repressing and inducing). The integrative analysis revealed genes potentially regulated by DNA methylation pointing out potential drivers and biomarkers related to PTC development.

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 Identification of an Autophagy-Related Signature Predicting Overall Survival for Papillary Thyroid Carcinoma

Dose-Response ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 155932581989926 ◽  
Author(s):  
Gang Hu ◽  
Hong-fang Feng ◽  
Hui Zhan
Keyword(s):  
Overall Survival ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Scoring System ◽  
Cox Regression ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Papillary Thyroid ◽  
Cox Regression Analysis

Background: Papillary thyroid carcinoma usually shows an excellent prognosis. However, its recurrence or persistence rate is high. In this study, we used bioinformatics to identify autophagy-related genes (ARGs) and establish a novel scoring system for papillary thyroid carcinoma. Methods: We collected ARGs sequencing data of patients with papillary thyroid carcinoma from The Cancer Genome Atlas database. Differentially expressed ARGs were identified by the “Limma” package in R language. After univariate and multivariate Cox regression analysis, an ARG signature was developed. The established prognostic signature was evaluated by Kaplan-Meier curve and time-dependent receiver operating characteristic. Results: A sum of 26 differentially expressed ARGs were identified. Gene set enrichment analysis revealed that several significantly oncological signatures were enriched, such as autophagy, p53 signaling pathway, apoptosis, human cytomegalovirus infection, and platinum drug resistance. After univariate and multivariate analysis, 3 ARGs ( ITPR1, CCL2, and CDKN2A) were selected to develop autophagy-related signature. Patients with high risk had significantly shorter overall survival than those with low risk. The areas under the curve indicated that the signature showed good accuracy of prediction. Conclusions: We established a novel scoring system based on 3 ARGs, which provides a promising tool for the development of personalized therapy.

scholarly journals Identification of Potential lncRNAs and miRNAs as Diagnostic Biomarkers for Papillary Thyroid Carcinoma Based on Machine Learning

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Fei Yang ◽  
Jie Zhang ◽  
Baokun Li ◽  
Zhijun Zhao ◽  
Yan Liu ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Epigenetic Modifications ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Endothelial Cell Migration ◽  
Papillary Thyroid ◽  
Diagnostic Biomarkers

Background. Papillary thyroid carcinoma (PTC) accounts for most of the proportion of thyroid cancer (TC). The objective of this study was to identify diagnostic, differentially expressed long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), contributing to understanding the epigenetics mechanism of PTC. Methods. The data of lncRNA, miRNA, and mRNA were downloaded from the Cancer Genome Atlas (TCGA) dataset, followed by functional analysis of differentially expressed mRNAs. Optimal diagnostic lncRNA and miRNA biomarkers were identified via random forest. The regulatory network between optimal diagnostic lncRNA and mRNAs and optimal diagnostic miRNA and mRNAs was identified, followed by the construction of ceRNA network of lncRNA-mRNA-miRNA. Expression validation and diagnostic analysis of lncRNAs, miRNAs, and mRNAs were performed. Overexpression of ADD3-AS1 was performed in PTC-UC3 cell lines, and cell proliferation and invasion assay were used for investigating the role of ADD3-AS1 in PTC. Results. A total of 107 differentially expressed lncRNAs, 81 differentially expressed miRNAs, and 515 differentially expressed mRNAs were identified. 11 lncRNAs and 6 miRNAs were regarded as the optimal diagnostic biomarkers for PTC. The epigenetic modifications via the above diagnostic lncRNAs and miRNAs were identified, including MIR181A2HG-FOXP2-hsa-miR-146b-3p, BLACAT1/ST7-AS1-RPS6KA5-hsa-miR-34a-5p, LBX2-AS1/MIR100HG-CDHR3-hsa-miR-34a-5p, ADD3-AS1-PTPRE-hsa-miR-9-5p, ADD3-AS1-TGFBR1-hsa-miR-214-3p, LINC00506-MMRN1-hsa-miR-4709-3p, and LOC339059-STK32A-hsa-miR-199b-5p. In the functional analysis, MMRN1 and TGFBR1 were involved in cell adhesion and endothelial cell migration, respectively. Overexpression of ADD3-AS1 inhibited cell growth and invasion in PTC cell lines. Conclusion. The identified lncRNAs/miRNAs/mRNA were differentially expressed between normal and cancerous tissues. In addition, identified altered lncRNAs and miRNAs may be potential diagnostic biomarkers for PTC. Additionally, epigenetic modifications via the above lncRNAs and miRNAs may be involved in tumorigenesis of PTC.

Exploration of DNA Methylation-Driven Genes in Papillary Thyroid Carcinoma Based on the Cancer Genome Atlas

2021 ◽  
Vol 28 (1) ◽  
pp. 99-114
Author(s):  
Yanwei Chen ◽  
Keke Wang ◽  
Mengyuan Shang ◽  
Shuangshuang Zhao ◽  
Zheng Zhang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Papillary Thyroid ◽  
Cancer Genome Atlas ◽  
Genome Atlas

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).

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 Loss of DNA methylation is related to increased expression of miR-21 and miR-146b in papillary thyroid carcinoma

2018 ◽  
Vol 10 (1) ◽  
Author(s):  
Isabella Maria Dias Payão Ortiz ◽  
Mateus Camargo Barros-Filho ◽  
Mariana Bisarro dos Reis ◽  
Caroline Moraes Beltrami ◽  
Fabio Albuquerque Marchi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Papillary Thyroid

scholarly journals TERT Promoter Mutations and Their Impact on Gene Expression Profile in Papillary Thyroid Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1597 ◽  
Author(s):  
Dagmara Rusinek ◽  
Aleksandra Pfeifer ◽  
Marta Cieslicka ◽  
Malgorzata Kowalska ◽  
Agnieszka Pawlaczek ◽  
...  
Keyword(s):  
Gene Expression ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Distant Metastases ◽  
Gene Set Enrichment Analysis ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Mutational Status

Background: Telomerase reverse transcriptase promoter (TERTp) mutations are related to a worse prognosis in various malignancies, including papillary thyroid carcinoma (PTC). Since mechanisms responsible for the poorer outcome of TERTp(+) patients are still unknown, searching for molecular consequences of TERTp mutations in PTC was the aim of our study. Methods: The studied cohort consisted of 54 PTCs, among them 24 cases with distant metastases. BRAF V600E, RAS, and TERTp mutational status was evaluated in all cases. Differences in gene expression profile between TERTp(+) and TERTp(−) PTCs were examined using microarrays. The evaluation of signaling pathways and gene ontology was based on the Gene Set Enrichment Analysis. Results: Fifty-nine percent (32/54) of analyzed PTCs were positive for at least one mutation: 27 were BRAF(+), among them eight were TERTp(+), and 1 NRAS(+), whereas five other samples harbored RAS mutations. Expression of four genes significantly differed in BRAF(+)TERTp(+) and BRAF(+)TERTp(−) PTCs. Deregulation of pathways involved in key cell processes was observed. Conclusions: TERTp mutations are related to higher PTC aggressiveness. CRABP2 gene was validated as associated with TERTp mutations. However, its potential use in diagnostics or risk stratification in PTC patients needs further studies.

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