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Identification of potential biomarkers and drugs for papillary thyroid cancer based on gene expression profile analysis.

ABSTRACT: The present study aimed to systematically examine the molecular mechanisms of papillary thyroid cancer (PTC), and identify potential biomarkers and drugs for the treatment of PTC. Two microarray data sets (GSE3467 and GSE3678), containing 16 PTC samples and 16 paired normal samples, were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified using the Linear Models for Microarray Analysis package. Subsequently, the common DEGs were screened for functional and pathway enrichment analysis using the Database for Annotation Visualization and Integrated Discovery. The representative interaction subnetwork was further derived using Molecular Complex Detection software. In addition, the potential drugs for the hub DEGs in the subnetwork were screened from DrugBank and the potential drug?like ligands, which interacted with genes, were selected using MTiOpenScreen. A total of 167 common DEGs, including 77 upregulated and 90 downregulated DEGs, were screened. The common DEGs were associated with the functions of plasma membrane, extracellular matrix, response to steroid hormone stimulus and cell adhesion, and the pathways of tyrosine metabolism and cell adhesion molecules were significantly enriched. A total of eight common DEGs (MET, SERPINA1, LGALS3, FN1, TNFRSF11B, LAMB3 and COL13A1) were involved in the subnetwork. The two drugs, lanoteplase and ocriplasmin, and four drugs, ??mercaptoethanol, recombinant ? 1?antitrypsin, PPL?100 and API, were found for FN1 and SERPINA1, respectively. The common DEGs identified may be potential biomarkers for PCT. FN1 and SERPINA1 may be involved in PTC by regulating epithelial?to?mesenchymal transition and responding to steroid hormone stimuli, respectively. Ocriplasmin, ??mercaptoethanol and recombinant ? 1?antitrypsin may be potential drugs for the treatment of PTC.

SUBMITTER: Qu T

PROVIDER: S-EPMC5355717 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Identification of potential biomarkers and drugs for papillary thyroid cancer based on gene expression profile analysis.

Qu Ting T Li Yan-Ping YP Li Xiao-Hong XH Chen Yan Y

Molecular medicine reports 20161019 6

The present study aimed to systematically examine the molecular mechanisms of papillary thyroid cancer (PTC), and identify potential biomarkers and drugs for the treatment of PTC. Two microarray data sets (GSE3467 and GSE3678), containing 16 PTC samples and 16 paired normal samples, were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified using the Linear Models for Microarray Analysis package. Subsequently, the common DEGs were screene ...[more]

PMID: 27779685

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Project description:BackgroundPapillary 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.MethodsThe 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.ResultsA 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.ConclusionThe 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.

Project description:BackgroundRecent studies have proposed several gene signatures as biomarkers for different grades of gliomas from various perspectives. However, most of these genes can only be used appropriately for patients with specific grades of gliomas.MethodsIn this study, we aimed to identify survival-relevant genes shared between glioblastoma multiforme (GBM) and lower-grade glioma (LGG), which could be used as potential biomarkers to classify patients into different risk groups. Cox proportional hazard regression model (Cox model) was used to extract relative genes, and effectiveness of genes was estimated against random forest regression. Finally, risk models were constructed with logistic regression.ResultsWe identified 104 key genes that were shared between GBM and LGG, which could be significantly correlated with patients' survival based on next-generation sequencing data obtained from The Cancer Genome Atlas for gene expression analysis. The effectiveness of these genes in the survival prediction of GBM and LGG was evaluated, and the average receiver operating characteristic curve (ROC) area under the curve values ranged from 0.7 to 0.8. Gene set enrichment analysis revealed that these genes were involved in eight significant pathways and 23 molecular functions. Moreover, the expressions of ten (CTSZ, EFEMP2, ITGA5, KDELR2, MDK, MICALL2, MAP 2 K3, PLAUR, SERPINE1, and SOCS3) of these genes were significantly higher in GBM than in LGG, and comparing their expression levels to those of the proposed control genes (TBP, IPO8, and SDHA) could have the potential capability to classify patients into high- and low- risk groups, which differ significantly in the overall survival. Signatures of candidate genes were validated, by multiple microarray datasets from Gene Expression Omnibus, to increase the robustness of using these potential prognostic factors. In both the GBM and LGG cohort study, most of the patients in the high-risk group had the IDH1 wild-type gene, and those in the low-risk group had IDH1 mutations. Moreover, most of the high-risk patients with LGG possessed a 1p/19q-noncodeletion.ConclusionIn this study, we identified survival relevant genes which were shared between GBM and LGG, and those enabled to classify patients into high- and low-risk groups based on expression level analysis. Both the risk groups could be correlated with the well-known genetic variants, thus suggesting their potential prognostic value in clinical application.

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Identification of potential biomarkers and drugs for papillary thyroid cancer based on gene expression profile analysis.

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Identification of potential biomarkers and drugs for papillary thyroid cancer based on gene expression profile analysis.

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