scholarly journals Five genes involved in circular RNA-associated competitive endogenous RNA network correlates with metastasis in papillary thyroid carcinoma

2021 ◽  
Vol 18 (6) ◽  
pp. 9016-9032
Author(s):  
Jie Qiu ◽  
◽  
Maolin Sun ◽  
Chuanshan Zang ◽  
Liwei Jiang ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Circular Rna ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Regulatory Mechanisms ◽  
Recursive Feature Elimination ◽  
Support Vector ◽  
Papillary Thyroid ◽  
Competitive Endogenous Rna

<abstract> <p>&gt;This study aimed to identify potential circular RNA (circRNA), microRNA (miRNA) and mRNA biomarkers as well as their underlying regulatory mechanisms in papillary thyroid carcinoma (PTC). Three microarray datasets from the Gene Expression Omnibus database as well as expression data and clinical phenotype from The Cancer Genome Atlas (TCGA) were downloaded, followed by differential expression, functional enrichment, protein–protein interaction (PPI), and module analyses. The support vector machine (SVM)-recursive feature elimination (RFE) algorithm was used to screen the key circRNAs. Finally, the mRNA-miRNA-circRNA regulatory network and competitive endogenous RNA (ceRNA) network were constructed. The prognostic value and clinical correlations of key mRNAs were investigated using TCGA dataset, and their expression was validated using the UALCAN database. A total of 1039 mRNAs, 18 miRNAs and 137 circRNAs were differentially expressed in patients with PTC. A total of 37 key circRNAs were obtained using the SVM-RFE algorithm, whereas 46 key mRNAs were obtained from significant modules in the PPI network. A total of 11 circRNA-miRNA pairs and 40 miRNA-mRNA pairs were predicted. Based on these interaction pairs, 46 circRNA-miRNA-mRNA regulatory pairs were integrated, of which 8 regulatory pairs in line with the ceRNA hypothesis were obtained, including two circRNAs (circ_0004053 and circ_0028198), three miRNAs (miR-199a-5p, miR-199b-5p, and miR-7-5p), and five mRNAs, namely <italic>APOA2</italic>, <italic>CCL20</italic>, <italic>LPAR5</italic>, <italic>MFGE8</italic>, and <italic>TIMP1</italic>. Survival analysis showed that <italic>LPAR5</italic> expression was associated with patient survival. <italic>APOA2</italic> expression showed significant differences between metastatic and non-metastatic tumors, whereas <italic>CCL20</italic>, <italic>LPAR5</italic>, <italic>MFGE8</italic> and <italic>TIMP1</italic> showed significant differences between metastatic and non-metastatic lymph nodes. Overall, we identified several potential targets and regulatory mechanisms involved in PTC. <italic>APOA2</italic>, <italic>CCL20</italic>, <italic>LPAR5</italic>, <italic>MFGE8</italic>, and <italic>TIMP1</italic> may be correlated with PTC metastasis.</p> </abstract>

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.

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.

Exosomal hsa-miR-129-2 and hsa-miR-889 from a 6-microRNA signature might be a potential biomarker for predicting prognosis of papillary thyroid carcinoma

2021 ◽  
Vol 24 ◽  
Author(s):  
Ying Xin ◽  
Kexin Meng ◽  
Haiwei Guo ◽  
Bin Chen ◽  
Chuanming Zheng ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
High Throughput ◽  
Messenger Rna ◽  
High Throughput Sequencing ◽  
The Cancer Genome Atlas ◽  
Papillary Thyroid ◽  
Control Groups ◽  
Potential Biomarker ◽  
And Control

Background: Papillary thyroid carcinoma (PTC) is a subtype of thyroid cancer with increasing incidence over time. Objective: This study aimed to build a risk score (RS) system for PTC patients. Methods: PTC microRNA (miRNA) and messenger RNA (mRNA) expression data were extracted from The Cancer Genome Atlas (TCGA) database. The 491 PTC samples were randomly divided into training and validation sets. Using the limma software package, differentially expressed mRNAs (DEGs) and miRNAs (DEMs) between the tumor and control groups were screened. In order to construct an RS system, a survival package was used to select independent miRNAs related to prognosis. Enrichment analysis was performed, and a miRNA-mRNA co-expression network was constructed. High-throughput sequencing was also used to verify the prognostic miRNAs in exosomes. Results: We found 1363 DEGs and 171 DEMs between the tumor and control groups. After identifying 26 DEMs that were significantly related to prognosis, 6 independent prognosis-associated miRNAs were selected to build an RS system. The areas under the curves of the overall survival rates of the training, validation, and entire sets were 0.847, 0.772, and 0.819, respectively. By conducting pathway analysis using the miRNA-mRNA co-expression network, one overlapping factor and five overlapping pathways were obtained. In addition, high-throughput sequencing revealed that the hsa-miR-129-2, hsa-miR-548j, hsa-miR-6734, and hsa-miR-889 expression levels in TCGA tumor tissues and exosomes were consistent, and those of hsa-miR-129-2 and hsa-miR-889 between patients and controls were significantly different in exosomes. Conclusion: The six-miRNA RS system in exosomes may comprise independent signatures for predicting PTC patient prognosis.

Progression Risk Assessment of Post-Surgical Papillary Thyroid Carcinoma Based on Circular RNA-Associated Competing Endogenous RNA Mechanisms

2020 ◽  
Author(s):  
Mengwei Wu ◽  
Rui Liu ◽  
Hongwei Yuan ◽  
Xiequn Xu ◽  
Xiaobin Li ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Assessment Tool ◽  
Cox Regression ◽  
Circular Rna ◽  
Differentially Expressed ◽  
Papillary Thyroid ◽  
Progression Risk ◽  
Stratification System

Abstract BackgroundAccurate risk assessment of post-surgical progression in papillary thyroid carcinoma (PTC) patients is critical. Exploring key differentially expressed mRNAs (DE-mRNAs) regulated by differentially expressed circRNAs (DE-circRNAs) via the ceRNA mechanism could help establish a novel assessment tool. MethodsceRNA network was established based on differentially expressed RNAs and correlation analysis. DE-mRNAs within the ceRNA network associated with progression-free interval (PFI) of PTC were identified to construct a prognostic ceRNA regulatory subnetwork. LASSO-Cox regression was applied to identify hub DE-mRNAs and establish a novel DE-mRNA signature in predicting PFI of PTC.ResultsSix hub DE-mRNAs, namely CLCNKB, FXBO27, FXYD6, RIMS2, SPC24, and CDKN2A, were identified to be most significantly related to the PFI of PTC and a prognostic DE-mRNA signature was proposed. A nomogram incorporating the DE-mRNA signature and clinical parameters was established to improve the progression risk assessment in post-surgical PTC, which was superior to the ATA risk stratification system and MACIS score AJCC staging system.ConclusionsBased on the circRNA-associated ceRNA RNA mechanism, a DE-mRNA signature and prognostic nomogram was established, which may improve the progression risk assessment in post-surgical PTC.

scholarly journals The Landscape of Circular RNA Expression Profiles in Papillary Thyroid Carcinoma Based on RNA Sequencing

2018 ◽  
Vol 47 (3) ◽  
pp. 1122-1132 ◽  
Author(s):  
Xiabin Lan ◽  
Jiajie Xu ◽  
Chao Chen ◽  
Chuanming Zheng ◽  
Jiafeng Wang ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Kegg Pathway ◽  
Expression Profiles ◽  
Roc Curves ◽  
Circular Rna ◽  
Papillary Thyroid ◽  
Biological Functions ◽  
Qrt Pcr ◽  
Potential Biomarkers

Background/Aims: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. However, the molecular mechanisms responsible for its tumorigenesis and progression remain largely unknown. Circular RNA (circRNA) is a novel type of noncoding RNA that can serve as an ideal biomarker due to its stability. Recent evidence suggests that circRNAs play important roles in tumorigenesis. This study aims to investigate circRNA expression profiles and their potential biological functions in PTC. Methods: High-throughput RNA sequencing was used to assess circRNA expression profiles in PTC, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate dysregulated circRNAs. Receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic value of circRNAs for PTC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were employed to determine the biological functions of differentially expressed circRNAs. Bioinformatic analyses were applied to predict interactions between circRNAs and microRNAs (miRNAs), and a circRNA-miRNA-mRNA network was constructed using Cytoscape software. Results: We identified a number of differentially expressed circRNAs in PTC tissues compared with paired normal thyroid tissues, with chr5: 160757890-160763776–, chr12: 40696591-40697936+, chr7: 22330794-22357656-, and chr21: 16386665-16415895– being upregulated, and chr7: 91924203-91957214+, chr2: 179514891-179516047–, chr9: 16435553-16437522–, and chr22: 36006931-36007153– being downregulated. These findings were confirmed by qRT-PCR, and ROC curves indicated that they can serve as potential biomarkers for PTC. GO and KEGG pathway analyses showed that some of these circRNAs are related to cancers. Additionally, bioinformatic analyses revealed a potential competing-endogenous-RNA-regulating network among circRNAs, miRNAs, and mRNAs. Conclusions: Our study results depict the landscape of circRNA expression profiles in PTC and also provide potential biomarkers for PTC. Further functional and mechanistic studies of these circRNAs may improve our understanding of PTC tumorigenesis.

scholarly journals Prognostic Implications of CD10 and CD15 Expression in Papillary Thyroid Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1413 ◽  
Author(s):  
Eun Ji Oh ◽  
Andrey Bychkov ◽  
Haejin Cho ◽  
Tae-Min Kim ◽  
Ja Seong Bae ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Risk Group ◽  
Thyroid Tissue ◽  
High Risk Group ◽  
The Cancer Genome Atlas ◽  
Prognostic Impact ◽  
Papillary Thyroid ◽  
Cd15 Expression ◽  
Cd10 Expression

Patients with papillary thyroid carcinoma (PTC) have excellent survival, but recurrence remains a major problem in the management of PTC. We aimed to determine the prognostic impact of the expression of CD10 and CD15 in patients with PTC. Immunohistochemistry for CD10 and CD15 was performed on the tissue microarrays of 515 patients with PTC. The expression of CD10 and CD15 was detected in 201 (39.0%) and 295 (57.3%) of 515 PTC cases, respectively, but not in the adjacent benign thyroid tissue. Recurrence was inversely correlated with CD15 expression (p = 0.034) but not with CD10 expression. In 467 PTC patients treated with radioiodine remnant ablation, the CD15 expression had an adjusted hazard ratio of 0.500 (p = 0.024) for recurrence-free survival and an adjusted odds ratio of 2.678 (p = 0.015) for predicting long-term excellent therapeutic response. CD10 expression was not associated with clinical outcomes. In the Cancer Genome Atlas dataset, the expression level of FUT4 (CD15) mRNA was higher in the low/intermediate-risk group for recurrence than in the high-risk group and exhibited positive correlation with SLC5A5 (NIS) mRNA expression (p = 0.003). Taken together, CD15 expression was identified as an independent prognostic marker for improved prognosis in PTC patients.

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