scholarly journals Systems Biology Approaches to Investigate Genetic and Epigenetic Molecular Progression Mechanisms for Identifying Gene Expression Signatures in Papillary Thyroid Cancer

2019 ◽  
Vol 20 (10) ◽  
pp. 2536
Author(s):  
Shan-Ju Yeh ◽  
Chien-Yu Lin ◽  
Cheng-Wei Li ◽  
Bor-Sen Chen

Thyroid cancer is the most common endocrine cancer. Particularly, papillary thyroid cancer (PTC) accounts for the highest proportion of thyroid cancer. Up to now, there are few researches discussing the pathogenesis and progression mechanisms of PTC from the viewpoint of systems biology approaches. In this study, first we constructed the candidate genetic and epigenetic network (GEN) consisting of candidate protein–protein interaction network (PPIN) and candidate gene regulatory network (GRN) by big database mining. Secondly, system identification and system order detection methods were applied to prune candidate GEN via next-generation sequencing (NGS) and DNA methylation profiles to obtain the real GEN. After that, we extracted core GENs from real GENs by the principal network projection (PNP) method. To investigate the pathogenic and progression mechanisms in each stage of PTC, core GEN was denoted in respect of KEGG pathways. Finally, by comparing two successive core signaling pathways of PTC, we not only shed light on the causes of PTC progression, but also identified essential biomarkers with specific gene expression signature. Moreover, based on the identified gene expression signature, we suggested potential candidate drugs to prevent the progression of PTC with querying Connectivity Map (CMap).

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Cong Zhang ◽  
Chunrui Bo ◽  
Lunhua Guo ◽  
Pingyang Yu ◽  
Susheng Miao ◽  
...  

Abstract Background The morbidity of thyroid carcinoma has been rising worldwide and increasing faster than any other cancer type. The most common subtype with the best prognosis is papillary thyroid cancer (PTC); however, the exact molecular pathogenesis of PTC is still not completely understood. Methods In the current study, 3 gene expression datasets (GSE3678, GSE3467, and GSE33630) and 2 miRNA expression datasets (GSE113629 and GSE73182) of PTC were selected from the Gene Expression Omnibus (GEO) database and were further used to identify differentially expressed genes (DEGs) and deregulated miRNAs between normal thyroid tissue samples and PTC samples. Then, Gene Ontology (GO) and pathway enrichment analyses were conducted, and a protein-protein interaction (PPI) network was constructed to explore the potential mechanism of PTC carcinogenesis. The hub gene detection was performed using the CentiScaPe v2.0 plugin, and significant modules were discovered using the MCODE plugin for Cytoscape. In addition, a miRNA-gene regulatory network in PTC was constructed using common deregulated miRNAs and DEGs. Results A total of 263 common DEGs and 12 common deregulated miRNAs were identified. Then, 6 significant KEGG pathways (P < 0.05) and 82 significant GO terms were found to be enriched, indicating that PTC was closely related to amino acid metabolism, development, immune system, and endocrine system. In addition, by constructing a PPI network and miRNA-gene regulatory network, we found that hsa-miR-181a-5p regulated the most DEGs, while BCL2 was targeted by the most miRNAs. Conclusions The results of this study suggested that hsa-miR-181a-5p and BCL2 and their regulatory networks may play important roles in the pathogenesis of PTC.


2020 ◽  
Vol 52 (10) ◽  
pp. 1166-1170
Author(s):  
Midie Xu ◽  
Tuanqi Sun ◽  
Shishuai Wen ◽  
Tingting Zhang ◽  
Xin Wang ◽  
...  

Oncogene ◽  
2004 ◽  
Vol 23 (44) ◽  
pp. 7436-7440 ◽  
Author(s):  
Milo Frattini ◽  
Cristina Ferrario ◽  
Paola Bressan ◽  
Debora Balestra ◽  
Loris De Cecco ◽  
...  

Blood ◽  
2008 ◽  
Vol 111 (11) ◽  
pp. 5371-5379 ◽  
Author(s):  
Christian Langer ◽  
Michael D. Radmacher ◽  
Amy S. Ruppert ◽  
Susan P. Whitman ◽  
Peter Paschka ◽  
...  

AbstractBAALC expression is considered an independent prognostic factor in cytogenetically normal acute myeloid leukemia (CN-AML), but has yet to be investigated together with multiple other established prognostic molecular markers in CN-AML. We analyzed BAALC expression in 172 primary CN-AML patients younger than 60 years of age, treated similarly on CALGB protocols. High BAALC expression was associated with FLT3-ITD (P = .04), wild-type NPM1 (P < .001), mutated CEBPA (P = .003), MLL-PTD (P = .009), absent FLT3-TKD (P = .005), and high ERG expression (P = .05). In multivariable analysis, high BAALC expression independently predicted lower complete remission rates (P = .04) when adjusting for ERG expression and age, and shorter survival (P = .04) when adjusting for FLT3-ITD, NPM1, CEBPA, and white blood cell count. A gene-expression signature of 312 probe sets differentiating high from low BAALC expressers was identified. High BAALC expression was associated with overexpression of genes involved in drug resistance (MDR1) and stem cell markers (CD133, CD34, KIT). Global microRNA-expression analysis did not reveal significant differences between BAALC expression groups. However, an analysis of microRNAs that putatively target BAALC revealed a potentially interesting inverse association between expression of miR-148a and BAALC. We conclude that high BAALC expression is an independent adverse prognostic factor and is associated with a specific gene-expression profile.


Blood ◽  
2010 ◽  
Vol 116 (7) ◽  
pp. 1092-1104 ◽  
Author(s):  
Fabrice Jardin ◽  
Jean-Philippe Jais ◽  
Thierry-Jo Molina ◽  
Françoise Parmentier ◽  
Jean-Michel Picquenot ◽  
...  

Abstract Genomic alterations play a crucial role in the development and progression of diffuse large B-cell lymphomas (DLBCLs). We determined gene copy number alterations (GCNAs) of TP53, CDKN2A, CDKN1B, BCL2, MYC, REL, and RB1 with a single polymerase chain reaction (PCR) assay (quantitative multiplex PCR of short fragments [QMPSF]) in a cohort of 114 patients with DLBCL to assess their prognostic value and relationship with the gene expression profile. Losses of TP53 and CDKN2A, observed in 8% and 35% of patients, respectively, were significantly associated with a shorter survival after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) treatment, independently of the International Prognostic Index and of the cell of origin. Analysis of the 9p21 genomic region indicated that transcripts encoding p14ARF and p16INK4A were both disrupted in most patients with CDKN2A deletion. These patients predominantly had an activated B-cell profile and showed a specific gene expression signature, characterized by dysregulation of the RB/E2F pathway, activation of cellular metabolism, and decreased immune and inflammatory responses. These features may constitute the molecular basis sustaining the unfavorable outcome and chemoresistance of this DLBCL subgroup. Detection of TP53 and CDKN2A loss by QMPSF is a powerful tool that could be used for patient stratification in future clinical trials.


2020 ◽  
Vol 35 (3) ◽  
pp. 656-668
Author(s):  
Seonhyang Jeong ◽  
In-Kyu Kim ◽  
Hyunji Kim ◽  
Moon Jung Choi ◽  
Jandee Lee ◽  
...  

2015 ◽  
Vol 2 (2) ◽  
pp. 87-91
Author(s):  
Mara Cașorte ◽  
Simona Elena Albu ◽  
R. Iorgulescu ◽  
Anda Dumitrașcu ◽  
Dana Terzea ◽  
...  

The thyroid cancer had an increasing frequency during the last decades mostly related to better and accessible detection methods. The papillary type has the major epidemiologic impact. We present a case with mixed symptoms before surgery, a rare combination of both thyrotoxicosis and thyroid malignancy and an unusual pathologic report in a 56-year-old female known with total hysterectomy at age of 42, diagnosed with toxic goiter 2 years ago and under intermittent therapy with thiamazol. She presented for unspecific hot flashes and palpitation at gynaecology and she was referred for endocrine evaluation that revealed unspecific cervical compression complains, and a large goiter. The Thyroid-Stimulating Hormone was normal under thiamazol and so were the thyroid antibodies and calcitonin. The computed tomography pointed an isthmus and left lobe nodule of maximum 7.28 cm with mass effect on trachea. Total thyroidectomy was performed without any significant complications. The patient was hospitalised for 4 days (less than 48 hours postoperatively). The pathological report showed a papillary thyroid cancer (stage III) with oxyphil variant and an insular and solid pattern component. A high proliferative index is detected by vessels invasion and a ki-67 of 15 %. She received radioiodine therapy and then she started suppression levothyroxine treatment. The insular and oxyphilic pattern as well as the large tumour size of 6 cm suggest a severe prognosis. On the other hand, it is still a matter of debate whether non-autoimmune hyperthyroidism and solid pathologic features subscribe to the hypothesis of an aggressive cancer phenotype. Lifelong follow up is needed.


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