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.

scholarly journals A Novel Prognostic Nomogram Based on Metastasis-Related Genes Signature for Predicting the Progression-free Interval in Patients With Papillary Thyroid Carcinoma

2021 ◽  
Author(s):  
Rui Liu ◽  
Mengwei Wu ◽  
Zhen Cao ◽  
Xiaobin Li ◽  
Hongwei Yuan ◽  
...  
Keyword(s):  
High Risk ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Gene Signature ◽  
Functional Enrichment ◽  
Clinical Parameters ◽  
Papillary Thyroid ◽  
High Risk Patients ◽  
Free Interval ◽  
Risk Patients

Abstract Background: The recurrence rate for papillary thyroid carcinoma (PTC) after surgery is high, which is a significant issue for patients regarding with low-grade malignancy. We built a novel predictive model with metastasis-related genes (MTGs) and relevant clinical parameters for predicting progression-free interval (PFI) after surgery for 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 14-gene signature using Lasso-Penalty regression. Finally, we established a signature and clinical parameters-based nomogram for predicting the PFI of PTC . We then validated the efficacy of the signature in marking off high risk patients; the nomogram's performance in predicting PFI was also evaluated with receiver operating characteristic (ROC) curve and Harrell's concordance index (C-index).Results: We identified 155 DE-MTGs related to PFI in PTC. The functional enrichment analysis showed that the DE-MTGs were associated with important oncogenic process. Consequently, we found a novel 14-gene signature. The 14-gene signature could distinguish patients with poorer prognosis and predicted PFI accurately. The signature was 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 superior to the current clinical risk evaluating system in predicting the recurrence of PTC. Conclusions: The 14-gene 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.

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.

Identification of key mRNAs, miRNAs, and mRNA-miRNA network involved in papillary thyroid carcinoma

2020 ◽  
Vol 15 ◽  
Author(s):  
Wei Han ◽  
Dongchen Lu ◽  
Chonggao Wang ◽  
Mengdi Cui ◽  
Kai Lu
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Differential Expression Analysis ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Integrated Analysis ◽  
Papillary Thyroid ◽  
Gene Set Enrichment ◽  
Mirna Expression Data

Background: In the past decades, the incidence of thyroid cancer (TC) has been gradually increasing, owing to the widespread use of ultrasound scanning devices. However, the key mRNAs, miRNAs, and mRNA-miRNA network in papillary thyroid carcinoma (PTC) has not been fully understood. Material and Methods: In this study, multiple bioinformatics methods were employed, including differential expression analysis, gene set enrichment analysis, and miRNA-mRNA interaction network construction. Results: First, we investigated the key miRNAs that regulated significantly more differentially expressed genes based on GSEA method. Second, we searched for the key miRNAs based on the mRNA-miRNA interaction subnetwork involved in PTC. We identified hsa-mir-1275, hsa-mir-1291, hsa-mir-206 and hsa-mir-375 as the key miRNAs involved in PTC pathogenesis. Conclusion: The integrated analysis of the gene and miRNA expression data not only identified key mRNAs, miRNAs, and mRNA-miRNA network involved in papillary thyroid carcinoma, but also improved our understanding of the pathogenesis of PTC.

scholarly journals SUN-132 KLF5 Is a Poor Prognostic Marker and Therapeutic Target for Middle Eastern Papillary Thyroid Carcinoma

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Khawla S Al-Kuraya ◽  
Abdul K Siraj ◽  
Pratheeshkumar Poyil ◽  
Divya Padmaja ◽  
Sandeep Kumar Parvathareddy ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Therapeutic Target ◽  
Critical Role ◽  
Dependent Manner ◽  
Papillary Thyroid ◽  
Inhibition Of Proliferation ◽  
Over Expression

Abstract Thyroid cancer is the second most common malignancy among females in Saudi Arabia, with Papillary thyroid carcinoma (PTC) accounting for 80-90%. The Kruppel-like factor 5 (Klf5) is a transcription factor that play a critical role in cell transformation, proliferation and oncogenesis. Immunohistochemical analysis of KLF5 was performed in 1219 PTC cases. KLF5 over-expression was noted in 65.1% (793/1219) of PTCs, and was significantly associated with tall-cell variant (p <0.0001), extrathyroidal extension (p = 0.0003), lymph node metastasis (p < 0.0001) and stage IV tumors (p < 0.0001). Significant association was also noted with HIF-1α over-expression (p = 0.0492). Interestingly, KLF5 over-expressing tumors showed poor disease-free survival (p = 0.0066). Functional studies in PTC cell lines showed that KLF5 co-immunoprecipitated with HIF-1α. Knockdown of KLF5 decreased the expression of HIF-1α while KLF5 was not affected by HIF-1α inhibition, suggesting that KLF5 is a functional upstream of HIF-1α. Down-regulation of KLF5 using specific inhibitor, ML264 or siRNA inhibited cell invasion and migration. In addition, treatment of PTC cell lines with ML264 resulted in inhibition of proliferation and induction of apoptosis in a dose-dependent manner. Furthermore, silencing of KLF5 significantly decreased the self-renewal ability of spheroids generated from PTC cells. Our findings confer that KLF5 may be a potential therapeutic target for the treatment of papillary thyroid cancer.

scholarly journals Differential glycolytic profile and Warburg effect in papillary thyroid carcinoma cell lines

2016 ◽  
Vol 36 (6) ◽  
pp. 3673-3681 ◽  
Author(s):  
Raquel Guimarães Coelho ◽  
Juliana De Menezes Cazarin ◽  
João Paulo Albuquerque Cavalcanti De Albuquerque ◽  
Bruno Moulin De Andrade ◽  
Denise P. Carvalho
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Warburg Effect ◽  
Carcinoma Cell ◽  
Papillary Thyroid ◽  
Carcinoma Cell Lines ◽  
Thyroid Carcinoma Cell ◽  
Papillary Thyroid Carcinoma Cell

scholarly journals Metabolomic Alterations in Thyrospheres and Adherent Parental Cells in Papillary Thyroid Carcinoma Cell Lines: A Pilot Study

2018 ◽  
Vol 19 (10) ◽  
pp. 2948 ◽  
Author(s):  
Paola Caria ◽  
Laura Tronci ◽  
Tinuccia Dettori ◽  
Federica Murgia ◽  
Maria Santoru ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Krebs Cycle ◽  
Metabolic Phenotype ◽  
Gas Chromatography Mass Spectrometry ◽  
Papillary Thyroid ◽  
Time Data ◽  
Krebs Cycle Intermediates ◽  
New Biomarkers

Papillary thyroid carcinoma (PTC), is characterized by a heterogeneous group of cells, including cancer stem cells (CSCs), crucially involved in tumor initiation, progression and recurrence. CSCs appear to have a distinct metabolic phenotype, compared to non-stem cancer cells. How they adapt their metabolism to the cancer process is still unclear, and no data are yet available for PTC. We recently isolated thyrospheres, containing cancer stem-like cells, from B-CPAP and TPC-1 cell lines derived from PTC of the BRAF-like expression profile class, and stem-like cells from Nthy-ori3-1 normal thyreocyte-derived cell line. In the present study, gas chromatography/mass spectrometry metabolomic profiles of cancer thyrospheres were compared to cancer parental adherent cells and to non cancer thyrospheres profiles. A statistically significant decrease of glycolytic pathway metabolites and variations in Krebs cycle metabolites was found in thyrospheres versus parental cells. Moreover, cancer stem-like cells showed statistically significant differences in Krebs cycle intermediates, amino acids, cholesterol, and fatty acids content, compared to non-cancer stem-like cells. For the first time, data are reported on the metabolic profile of PTC cancer stem-like cells and confirm that changes in metabolic pathways can be explored as new biomarkers and targets for therapy in this tumor.

scholarly journals Ligands for Peroxisome Proliferator-Activated Receptor γ Inhibit Growth and Induce Apoptosis of Human Papillary Thyroid Carcinoma Cells

2001 ◽  
Vol 86 (5) ◽  
pp. 2170-2177 ◽  
Author(s):  
Kazuyasu Ohta ◽  
Toyoshi Endo ◽  
Kazutaka Haraguchi ◽  
Jerome M. Hershman ◽  
Toshimasa Onaya
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cell Lines ◽  
Carcinoma Cell ◽  
Carcinoma Cells ◽  
Human Thyroid ◽  
Peroxisome Proliferator ◽  
Papillary Thyroid ◽  
Peroxisome Proliferator Activated Receptor ◽  
Carcinoma Cell Lines

Ligands for peroxisome proliferator-activated receptor γ (PPARγ) induce apoptosis and exert antiproliferative effects on several carcinoma cell lines. The present study investigates the expression of PPARγ and the possibility that agonists for PPARγ also inhibit the growth of human thyroid carcinoma cells. We examined this hypothesis using six cell lines, designated BHP thyroid carcinoma cells, which originated from patients with papillary thyroid carcinoma. RT-PCR analysis revealed that the thyroid carcinoma cell lines BHP2–7, 7–13, 10–3, and 18–21 express PPARγ. More PPARγ was expressed in carcinoma than in adjacent normal thyroid tissue in three of six samples of human papillary carcinoma of the thyroid. PPARγ-positive thyroid carcinoma cells were treated with agonists of PPARγ, troglitazone, BRL 49653, and 15-deoxy-Δ12,14-prostaglandin J2. Troglitazone (10μ mol/L), BRL 49653 (10 μmol/L), and 15-deoxy-Δ12,14-prostaglandin J2 (1 μg/mL) decreased[ 3H]thymidine incorporation and reduced cell number, respectively, in BHP carcinoma cell lines that expressed PPARγ. Under low serum conditions, ligands for PPARγ induced condensation of the nucleus and fragmentation of chromatin into nucleosome ladders. These findings indicate that the death of thyroid carcinoma cells is a form of apoptosis. To investigate the molecular mechanism of the apoptosis, we assessed expression of the apoptosis-regulatory genes bcl-2, bax, and c-myc. Troglitazone significantly increased the expression of c-myc messenger RNA but had no effect on the expression of bcl-2 and bax in thyroid carcinoma cells. These results suggest that, at least in part, the induction of apoptosis in human papillary thyroid carcinoma cells may be due to an increase of c-myc. Troglitazone (500 mg/kg·day) significantly inhibited tumor growth and prevented distant metastasis of BHP18–21 tumors in nude mice in vivo. Taken together, these results suggest that PPARγ agonist inhibit cell growth of some types of human thyroid cancer.

scholarly journals Identification of Latent Diagnostic Biomarkers and Biological Pathways in Dermatomyositis Based on WGCNA

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Shaxi Ouyang ◽  
Yifang Liu ◽  
Changjuan Xiao ◽  
Qinghua Zeng ◽  
Xun Luo ◽  
...  
Keyword(s):  
Cell Lines ◽  
Differentially Expressed Gene ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Receptor Interaction ◽  
Interferon Α ◽  
Pathway Enrichment Analysis ◽  
Oligoadenylate Synthetase

Introduction. Dermatomyositis (DM) is a chronic autoimmune disease of predominantly lymphocytic infiltration mainly involving the transverse muscle. Its pathogenesis is remaining unknown. This research is designed to probe the latent pathogenesis of dermatomyositis, identify potential biomarkers, and reveal the pathogenesis of dermatomyositis through information biology analysis of gene chips. Methods. In this study, we utilised the GSE14287 and GSE11971 datasets rooted in the Gene Expression Omnibus (GEO) databank, which included a total of 62 DM samples and 9 normal samples. The datasets were combined, and the differentially expressed gene sets were subjected to weighted gene coexpression network analysis, and the hub gene was screened using a protein interaction network from genes in modules highly correlated with dermatomyositis progression. Results. A total of 3 key genes—myxovirus resistance-2 (MX2), oligoadenylate synthetase 1 (OAS1), and oligoadenylate synthetase 2 (OAS2)—were identified in combination with cell line samples, and the expressions of the 3 genes were verified separately. The results showed that MX2, OAS1, and OAS2 were highly expressed in LPS-treated cell lines compared to normal cell lines. The results of pathway enrichment analysis of the genes indicated that all 3 genes were enriched in the cytosolic DNA signalling and cytokine and cytokine receptor interaction signalling pathways; the results of functional enrichment analysis showed that all 3 were enriched in interferon-α response and interferon-γ response functions. Conclusions. This is important for the study of the pathogenesis and objective treatment of dermatomyositis and provides important reference information for the targeted therapy of dermatomyositis.

scholarly journals Altered molecular pathways and prognostic markers in active systemic juvenile idiopathic arthritis: integrated bioinformatic analysis

2021 ◽  
Author(s):  
Yi Ren ◽  
Hannah Labinsky ◽  
Andriko Palmowski ◽  
Henrik Bäcker ◽  
Michael Müller ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Prognostic Markers ◽  
Treatment Success ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Decisive Role ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Bioinformatic Analysis ◽  
Functional Enrichment ◽  
Cellular Pathogenesis

Systemic juvenile idiopathic arthritis (SJIA) is a severe childhood-onset inflammatory disease characterized by arthritis accompanied by systemic auto-inflammation and extra-articular symptoms. While recent advances have unraveled a range of risk factors, the pathomechanisms involved in SJIA and potential prognostic markers for treatment success remain partly unknown. In this study, we included 70 active SJIA and 55 healthy control patients from the National Center for Biotechnology Information to analyze for differentially expressed genes (DEGs) using R. Functional enrichment analysis, protein-protein interaction (PPI), and gene module construction were performed for DEGs and hub gene set. We additionally examined immune system cell composition with CIBERSORT and predicted prognostic markers and potential treatment drugs for SJIA. In total, 94 upregulated and 24 downregulated DEGs were identified. Two specific modules of interest and eight hub genes (ARG1, DEFA4, HP, MMP8, MMP9, MPO, OLFM4, PGLYRP1) were screened out. Functional enrichment analysis suggested that complex neutrophil-related functions play a decisive role in the disease pathogenesis. CIBERSORT indicated neutrophils, M0 macrophages, CD8+ T cells, and naïve B cells to be relevant drivers of disease progression. Additionally, we identified TPM2 and GZMB as potential prognostic markers for treatment response to canakinumab. Moreover, sulindac sulfide, (-)-catechin, and phenanthridinone were identified as promising treatment agents. This study provides a new insight into molecular and cellular pathogenesis of active SJIA and highlights potential targets for further research.

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