scholarly journals Exploring Somatic Alteration Associating With Aggressive Behaviors of Papillary Thyroid Carcinomas by Targeted Sequencing

2021 ◽  
Vol 11 ◽  
Author(s):  
Yi Li ◽  
Wei Gao ◽  
Xiaojun Cai ◽  
Anqi Jin ◽  
Jian Shen ◽  
...  
Keyword(s):  
High Frequency ◽  
Treatment Plan ◽  
Variant Calling ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Papillary Thyroid ◽  
Event Free Survival ◽  
Gene Markers ◽  
Free Survival ◽  
Mutant Genes

Wisely differentiating high-risk papillary thyroid carcinoma (PTC) patients from low-risk PTC patients preoperatively is necessary when comes to making a personalized treatment plan. It is not easy to stratify the risk of patients according to sonography or lab results before surgery. This study aims to seek out potential mutation gene markers that may be helpful in stratifying the risk of PTC. A custom panel of 439 PTC relevant and classic tumor metabolic pathway relevant genes was designed. Targeted capture sequencing was performed on 35 pairs of samples from 35 PTC tumors and 35 para-tumor thyroid tissues obtained during surgery. Variant calling and detection of cancer gene mutations were identified by bio-information analysis. Ingenuity Pathway Analysis (IPA) was performed to do functional enrichment analysis of high-frequency mutant genes. Immunohistochemistry (IHC) was performed on 6 PTC patients to explore the expression of protein associated with interested genes. Event-free survival (EFS) was calculated to determine which genes might affect the prognosis of patients. We have identified 32 high-frequency mutant genes in PTC including BRAF. RBL2 was found to be significantly correlated to event-free survival, FOXO1, MUC6, PCDHB9, NOTCH1, FIZ1, and RTN1 were significantly associated with EFS, while BRAF mutant was not correlated to any of the prognosis indicators. Our findings in this study might open more choices when designing thyroid gene panels used in FNA samples to diagnose PTC and predict the potentially aggressive behavior of PTC.

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.

scholarly journals Identification of Key Genes Associated With the Process of Hepatitis B Inflammation and Cancer Transformation by Integrated Bioinformatics Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Jingyuan Zhang ◽  
Xinkui Liu ◽  
Wei Zhou ◽  
Shan Lu ◽  
Chao Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B ◽  
Differential Expression ◽  
Chronic Inflammation ◽  
Differential Expression Analysis ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Gene Markers ◽  
Key Genes

BackgroundHepatocellular carcinoma (HCC) has become the main cause of cancer death worldwide. More than half of hepatocellular carcinoma developed from hepatitis B virus infection (HBV). The purpose of this study is to find the key genes in the transformation process of liver inflammation and cancer and to inhibit the development of chronic inflammation and the transformation from disease to cancer.MethodsTwo groups of GEO data (including normal/HBV and HBV/HBV-HCC) were selected for differential expression analysis. The differential expression genes of HBV-HCC in TCGA were verified to coincide with the above genes to obtain overlapping genes. Then, functional enrichment analysis, modular analysis, and survival analysis were carried out on the key genes.ResultsWe identified nine central genes (CDK1, MAD2L1, CCNA2, PTTG1, NEK2) that may be closely related to the transformation of hepatitis B. The survival and prognosis gene markers composed of PTTG1, MAD2L1, RRM2, TPX2, CDK1, NEK2, DEPDC1, and ZWINT were constructed, which performed well in predicting the overall survival rate.ConclusionThe findings of this study have certain guiding significance for further research on the transformation of hepatitis B inflammatory cancer, inhibition of chronic inflammation, and molecular targeted therapy of cancer.

scholarly journals T-Box Transcription Factor 22 Is an Immune Microenvironment-Related Biomarker Associated With the BRAFV600E Mutation in Papillary Thyroid Carcinoma

2020 ◽  
Vol 8 ◽  
Author(s):  
Xubin Dong ◽  
Jingjing Song ◽  
Jing Hu ◽  
Cheng Zheng ◽  
Xiaohua Zhang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
T Regulatory Cells ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Papillary Thyroid ◽  
Immune Microenvironment ◽  
Invasion And Migration ◽  
T Box ◽  
Normal Tissues

Papillary thyroid cancer (PTC) is the most common malignant disease in endocrine systems. T-box transcription factor 22 (TBX22) is a phylogenetically conserved family member that has not been widely characterized in cancers. In this study, we explored the potential clinical significance and biological functions of TBX22 in PTC. Comprehensive analyses of TBX22 were based on the public databases and our local qRT-PCR cohort. We observed that TBX22 was significantly downregulated in PTC compared with normal tissues. TBX22 was associated with several clinicopathological factors in PTC. Low TBX22 expression correlated with BRAFV600E and TERT mutation. Functional enrichment analysis revealed that cancer-related pathways and immune progress were closely associated with TBX22 in PTC. In TBX22-low PTC, high immune infiltration levels with increased CD8+ T cells, natural killer, M1 macrophages, and T-regulatory cells were observed. TBX22 was negatively correlated with the activity of different steps of the anticancer immunity cycle. Functionally, overexpression of TBX22 inhibited the proliferation, invasion, and migration in PTC cells, while knocking down of TBX22 showed the opposite effects. The present findings disclose that TBX22, as an immune microenvironment-related biomarker, could be an important tumor suppresser gene and might inform the management of PTC patients better.

scholarly journals Pathogenic Variants Associated with Dilated Cardiomyopathy Predict Outcome in Pediatric Myocarditis

2021 ◽  
Author(s):  
Franziska Seidel ◽  
Manuel Holtgrewe ◽  
Nadya Al-Wakeel-Marquard ◽  
Bernd Opgen-Rhein ◽  
Josephine Dartsch ◽  
...  
Keyword(s):  
Heart Failure ◽  
Dilated Cardiomyopathy ◽  
Enrichment Analysis ◽  
Event Free Survival ◽  
Genetic Characteristics ◽  
Free Survival ◽  
Coronary Syndrome ◽  
Pathogenic Variants ◽  
Common Causes ◽  
Significant Enrichment

Background - Myocarditis is one of the most common causes leading to heart failure in children and a possible genetic background has been postulated. We sought to characterize the clinical and genetic characteristics in patients with myocarditis ≤18 years of age to predict outcome. Methods - A cohort of 42 patients (MYCPEDIG) with biopsy-proven myocarditis underwent genetic testing with targeted panel sequencing of cardiomyopathy-associated genes. MYCPEDIG patients were divided into subgroups according to the phenotype of dilated cardiomyopathy (DCM) at presentation, resulting in 22 patients without DCM (MYC-NonDCM) and 20 patients with DCM (MYC-DCM). Results - MYC-DCM patients (median age 1.4 years) were younger than MYC-NonDCM patients (median age 16.1 years; p<0.001) and were corresponding to heart failure-like and coronary syndrome-like phenotypes, respectively. At least one likely pathogenic/pathogenic (LP/P) variant was identified in 9/42 patients (22%), 8 of them were heterozygous, and 7/9 were in MYC-DCM. LP/P variants were found in genes validated for primary DCM ( BAG3 , DSP , LMNA , MYH7 , TNNI3 , TNNT2 , and TTN ). Rare variant enrichment analysis revealed significant accumulation of high impact disease variants in MYC-DCM versus healthy individuals (p=0.0003). Event-free survival was lower (p=0.008) in MYC-DCM patients compared to MYC-NonDCM and primary DCM. Conclusions - We report heterozygous LP/P variants in biopsy-proven pediatric myocarditis. Myocarditis patients with DCM phenotype were characterized by early-onset heart failure, significant enrichment of LP/P variants, and poor outcome. These phenotype- and age-group specific findings will be useful for personalized management of these patients. Genetic evaluation in children newly diagnosed with myocarditis and DCM phenotype is warranted.

scholarly journals Whole-genome sequencing of a Brazilian naturalized horse breed resistant to arid climate for identifying single nucleotide variants and insertions/deletions

2020 ◽  
Author(s):  
Danielle Cunha Cardoso ◽  
Eduardo Geraldo Alves Coelho ◽  
Brenda Neves Porto ◽  
glacy silva ◽  
Denea de Araújo Fernandes Pires ◽  
...  
Keyword(s):  
Variant Calling ◽  
Olfactory Receptors ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Single Nucleotide Variants ◽  
Horse Breed ◽  
Single Nucleotide ◽  
Arid Conditions ◽  
Single Nucleotide Variations

Abstract Background: In this study, we perform a search for variants (SNVs and InDels) in the genome of a Brazilian Naturalized horse breed, using FreeBayes and GATK variant calling tools. This breed presents exclusive adaptive traits of extreme importance to semi-arid conditions, such as those that allow survival under excessive sunlight, rainfall, low forage availability and stony ground. Moreover, these traits are expressed without any detriment to the performance and perpetuation of the breed. Results: A total of 305,588,364 reads were mapped in the horse reference genome, 1,598,210 single nucleotide variations and 138,139 insertions/deletions were detected by FreeBayes, 88,838 (SNVs) and 25,232 (InDels) by GATK. Both have been used in order to increase the safety of variant calls, identify in which regions of the genome they are present and check for variants in genes possibly associated with the peculiar traits exhibited by the breed. Conclusions: The variants annotation identified numerous non-synonymous SNVs and frameshift InDels, which could affect phenotypic variation. We found 28 and 392 Emsembl gene IDs containing high and moderate impact SNVs, including GTPase family members, olfactory receptors, mitochondrial complex and defense genes. Functional enrichment analysis was performed and revealed that variants in the olfactory transduction pathway were overrepresented.

scholarly journals ARHGAP11A Is a Prognostic Biomarker and Correlated With Immune Infiltrates in Gastric Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Biao Fan ◽  
Ke Ji ◽  
Zhaode Bu ◽  
Ji Zhang ◽  
Heli Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Prognostic Biomarker ◽  
Lymphocyte Activation ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Gene Markers ◽  
Division Cell

Background: ARHGAP11A, belongs to RhoGAPs family, is vital for cell motility. However, the role of ARHGAP11A in gastric cancer is obscure.Methods: The expression level of ARHGAP11A was analyzed by Oncomine database. The correlation of ARHGAP11A expression with immune infiltrates and associated gene markers was clarified by Tumor IMmune Estimation Resource and Gene Expression Profiling Interactive Analysis database. The correlation between ARHGAP11A expression and the patient prognosis was identified by Kaplan-Meier plotter and PrognoScan. Genetic changes of ARHGAP11A were analyzed by cBioPortal. The protein-protein interaction network and gene functional enrichment analysis were constructed and performed by GeneMANIA and Metascape.Results: We found that the expression levels of ARHGAP11A were elevated in various cancers including gastric cancer when compared with normal tissues. High expression of ARHGAP11A was significantly correlated with a better prognosis in gastric cancer. We revealed that the expression of ARHGAP11A was negatively associated with infiltration levels of CD8+ T cells, CD4+ T cells, macrophages and dendritic cells. In addition, ARHGAP11A expression was significantly correlated with gene markers of these immune cells. Lastly, gene functional enrichment analysis indicated that ARHGAP11A involved in regulating lymphocyte activation, cell division, cell killing, myeloid leukocyte differentiation and leukocyte apoptosis.Conclusion: Our findings demonstrated that ARHGAP11A was a valuable prognostic biomarker in gastric cancer. Further work is needed to validate its role and underlying mechanisms in regulating immune infiltrates.

Results of treatment of malignant germ cell tumors in 93 children: a report from the Childrens Cancer Study Group.

1991 ◽  
Vol 9 (10) ◽  
pp. 1782-1792 ◽  
Author(s):  
A R Ablin ◽  
M D Krailo ◽  
N K Ramsay ◽  
M H Malogolowkin ◽  
H Isaacs ◽  
...  
Keyword(s):  
Germ Cell ◽  
Treatment Plan ◽  
Germ Cell Tumors ◽  
Event Free Survival ◽  
Histologic Subtype ◽  
Free Survival ◽  
Results Of Treatment ◽  
Second Look ◽  
Incomplete Removal ◽  
Malignant Germ Cell Tumors

We report treatment results in 93 children entered on study from 1978 to 1984 with malignant germ cell tumors (MGCTs), excluding dysgerminoma and tumors of the testis or brain. The estimated 4-year survival and event-free survival (EFS) for all 93 patients were 54% and 49%, respectively. For 30 children with ovarian tumors, the estimated 4-year survival was 67% and EFS was 63%. For 63 children with nongonadal tumors, survival and EFS were 48% and 42%, respectively. The comparison of EFS between ovarian and nongonadal tumors was significant at P = .03. The treatment plan included a second-look surgical procedure after 18 weeks of chemotherapy. Over half of 36 patients evaluated as having a residual mass present immediately before second-look surgery had no malignant tumor after review of surgical specimens. Age greater than 11 years at diagnosis, incomplete removal of tumor at first surgery, and more than one structure or organ involved at diagnosis increased the risk for adverse event. The histologic subtype of the primary tumor was not related to outcome. Diagnosis was verified by independent pathologic review, and treatment was uniform. Seventeen percent of all registered patients (21 of 127) were excluded because of ineligible pathologic diagnoses; sixty percent (13 of 21) were immature teratomas.

scholarly journals Increased Expression of Integrin Subunit α3 is Correlated with Worse Recurrence-Free Survival in Thyroid Cancer

2021 ◽  
Author(s):  
Jun-jie Ma ◽  
Cheng Xiang ◽  
Heng-qing Zhu ◽  
Bing-long Bai ◽  
Ping Wang
Keyword(s):  
Regression Analysis ◽  
Cox Regression ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Genetic Alterations ◽  
Functional Enrichment ◽  
Integrin Subunit ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis

Abstract Objective: To investigate the potential effect of integrin subunit α3 (ITGA3) on thyroid cancer (THCA). Materials and Methods: Based on bioinformatics databases, the expression levels of ITGA3 were firstly analyzed, followed by evaluating the prognostic significance of ITGA3 in THCA patients. Cox regression analysis predicted the independent prognostic factors for THCA. Then, cBioportal and GSCA databases were applied to evaluate genetic alterations of ITGA3. Functional enrichment analysis was conducted using the R package. Finally, the upstream microRNAs of ITGA3 were determined. Results: ITGA3 gene and protein levels were higher in the THCA group than normal group (all P <0.05). And ITGA3 mRNA expression was significantly related to cancer stage and histological subtype (all P <0.01). Moreover, high expression of ITGA3 was associated with poor recurrence-free survival (RFS) of THCA patients in all subgroups (all P <0.01). Cox regression analysis presented that ITGA3 overexpression was an independent prognostic factor for worse RFS in THCA patients. Besides, significant relations were observed between ITGA3 and genetic alterations (FDR <0.01). Functional enrichment analysis indicated ECM-receptor interaction, and cell adhesion molecules were the shared regulatory pathways. We also found that ITGA3 might be the target gene of hsa-miR-3129, hsa-miR-181d, hsa-miR-181b, hsa-miR-199a, and hsa-miR-199b, which were all correlated with THCA patient prognosis. Conclusions: ITGA3 could be a reliable biomarker and promising therapeutic target for improving the diagnosis and clinical outcomes of THCA patients.

scholarly journals Comprehensive Identification of Potential Crucial Genes and miRNA-mRNA Regulatory Networks in Papillary Thyroid Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-25
Author(s):  
Ben-yu Nan ◽  
Guo-Feng Xiong ◽  
Zi-Rui Zhao ◽  
Xi Gu ◽  
Xin-Sheng Huang
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Regulatory Networks ◽  
Thyroid Nodules ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Papillary Thyroid ◽  
Ppi Network ◽  
Hub Genes ◽  
Age Related

Background. Thyroid cancer is the most common endocrine malignancy, with a recent global increase of 20% in age-related incidence. Ultrasonography and ultrasonography-guided fine-needle aspiration biopsy (FNAB) are the most widely used diagnostic tests for thyroid nodules; however, it is estimated that up to 25% of thyroid biopsies are cytologically inconclusive. Molecular markers can help guide patient-oriented and targeted treatment of thyroid nodules and thyroid cancer. Methods. Datasets related to papillary thyroid cancer (PTC) or thyroid carcinoma (GSE129562, GSE3678, GSE54958, GSE138042, and GSE124653) were downloaded from the GEO database and analysed using the Limma package of R software. For functional enrichment analysis, the Kyoto Encyclopedia of Genes and Genomes pathway analysis and Gene Ontology were applied to differentially expressed genes (DEGs) using the Metascape website. A protein-protein interaction (PPI) network was built from the STRING database. Gene expression, protein expression, immunohistochemistry, and potential functional gene survival were analysed using the GEPIA website, the Human Protein Atlas website, and the UALCAN website. Potential target miRNAs were predicted using the miRDB and Starbase datasets. Results. We found 219 upregulated and 310 downregulated DEGs, with a cut-off of p < 0.01 and ∣ log   FC ∣ > 1.5 . The DEGs in papillary thyroid cancer were mainly enriched in extracellular structural organisation. At the intersection of the PPI network and Metascape MCODEs, the hub genes in common were identified as FN1, APOE, CLU, and SDC2. In the targeted regulation network of miRNA-mRNA, the hsa-miR-424-5p was found to synchronously modulate two hub genes. Survival analysis showed that patients with high expression of CLU and APOE had better prognosis. Conclusions. CLU and APOE are involved in the molecular mechanism of papillary thyroid cancer. The hsa-miR-424-5p might have the potential to reverse the processes of papillary thyroid cancer by modulating the hub genes. These are potential targets for the treatment of patients with papillary thyroid cancer.

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