Analysis of Genetic Alterations Related to DNA Methylation in Testicular Germ Cell Tumors Based on Data Mining

2021 ◽  
pp. 1-12
Author(s):  
Xiaqing Yu ◽  
Yali Han ◽  
Simin Liu ◽  
Wen Jiang ◽  
Yingchun Song ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Germ Cell ◽  
Mrna Expression ◽  
Germ Cell Tumors ◽  
Genetic Alterations ◽  
Growth Patterns ◽  
The Cancer Genome Atlas ◽  
Testicular Germ Cell ◽  
Clinical Prognosis ◽  
Differentially Methylated Genes

Embryonal carcinoma (EC) and seminoma (SE) are both derived from germ cell neoplasia in situ but show big differences in growth patterns and clinical prognosis. Epigenetic regulation may play an important role in the development of EC and SE. This study investigated the DNA methylation-based genetic alterations between EC and SE by analyzing the datasets of mRNA expression and DNA methylation profiling. The datasets were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified between EC and SE by limma package in R environment. Gene function enrichment analysis of the DEGs was performed on the DAVID tool, the results of which suggested differences in capability of pluripotency and genomic stability between EC and SE. The minfi package and wANNOVAR tool were used to identify differentially methylated genes. A total of 37 genes were discovered with both mRNA expression and the accordant DNA methylation changes. The findings were verified by the sequencing data from The Cancer Genome Atlas database, and Kaplan-Meier survival analysis was performed. Finally, 5 genes (<i>PRDM1</i>, <i>LMO2</i>, <i>FAM53B</i>, <i>HCN4</i>, and <i>FAM124B</i>) were found that showed both low expression and high methylation in EC, and were significantly associated with relapse-free survival. The findings of methylation-based genetic features between EC and SE might be helpful in studying the role of DNA methylation in cancer development.

scholarly journals DNA methylation profiling as a tool for testicular germ cell tumors subtyping

Epigenomics ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1511-1523 ◽  
Author(s):  
Ana L Costa ◽  
Catarina Moreira-Barbosa ◽  
João Lobo ◽  
Bárbara Vilela-Salgueiro ◽  
Mariana Cantante ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Dna Methylation Profiling ◽  
Methylation Profiling

scholarly journals A network-based approach to identify DNA methylation and its involved molecular pathways in testicular germ cell tumors

2019 ◽  
Vol 10 (4) ◽  
pp. 893-902 ◽  
Author(s):  
Hao Bo ◽  
Ke Cao ◽  
Ruiling Tang ◽  
Han Zhang ◽  
Zhaojian Gong ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
Molecular Pathways ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell

scholarly journals Distinct telomere length and molecular signatures in seminoma and non-seminoma of testicular germ cell tumor

2018 ◽  
Vol 20 (4) ◽  
pp. 1502-1512 ◽  
Author(s):  
Hua Sun ◽  
Pora Kim ◽  
Peilin Jia ◽  
Ae Kyung Park ◽  
Han Liang ◽  
...  
Keyword(s):  
Germ Cell ◽  
Telomere Length ◽  
Complex Disease ◽  
Expression Profiles ◽  
Germ Cell Tumors ◽  
Telomerase Activity ◽  
The Cancer Genome Atlas ◽  
Testicular Germ Cell ◽  
Telomere Elongation ◽  
Yamanaka Factors

AbstractTesticular germ cell tumors (TGCTs) are classified into two main subtypes, seminoma (SE) and non-seminoma (NSE), but their molecular distinctions remain largely unexplored. Here, we used expression data for mRNAs and microRNAs (miRNAs) from The Cancer Genome Atlas (TCGA) to perform a systematic investigation to explain the different telomere length (TL) features between NSE (n = 48) and SE (n = 55). We found that TL elongation was dominant in NSE, whereas TL shortening prevailed in SE. We further showed that both mRNA and miRNA expression profiles could clearly distinguish these two subtypes. Notably, four telomere-related genes (TelGenes) showed significantly higher expression and positively correlated with telomere elongation in NSE than SE: three telomerase activity-related genes (TERT, WRAP53 and MYC) and an independent telomerase activity gene (ZSCAN4). We also found that the expression of genes encoding Yamanaka factors was positively correlated with telomere lengthening in NSE. Among them, SOX2 and MYC were highly expressed in NSE versus SE, while POU5F1 and KLF4 had the opposite patterns. These results suggested that enhanced expression of both TelGenes (TERT, WRAP53, MYC and ZSCAN4) and Yamanaka factors might induce telomere elongation in NSE. Conversely, the relative lack of telomerase activation and low expression of independent telomerase activity pathway during cell division may be contributed to telomere shortening in SE. Taken together, our results revealed the potential molecular profiles and regulatory roles involving the TL difference between NSE and SE, and provided a better molecular understanding of this complex disease.

scholarly journals Identification of Methylation Driven Biomarkers for Diagnosis and Prognosis in Colon Cancer by Integrative Analysis of TCGA, GTEx, and GEO Data

2021 ◽  
Author(s):  
Lichao Cao ◽  
Erfei Chen ◽  
Jin Yang
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Mrna Expression ◽  
Cox Regression ◽  
Integrative Analysis ◽  
The Cancer Genome Atlas ◽  
Expression Data ◽  
Cox Regression Analysis ◽  
Diagnosis And Prognosis ◽  
Differentially Methylated Genes

Abstract Background: The intention of the present work was to investigate methylation driven biomarkers for diagnosis and prognosis in colorectal cancer (CRC) by integrative analysis of DNA methylation and gene expression data from The Cancer Genome Atlas (TCGA), The Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO). Methods and Results: The differentially expression genes (DEGs) and differentially methylated genes (DMGs) were screened using mRNA expression and DNA methylation data from TCGA, respectively. And the methylation driven genes (MDGs) of CRC were further identified using MethylMix R package. Subsequently, the MDGs were underwent Random Forest (RF) analyses to establish diagnosis prediction model using mRNA expression data from TCGA and GTEx, which were then validated by GSE39582 from GEO dataset. In addition, prognostic biomarkers that were used to establish the methylation related risk score model was generated by the univariate and multivariate Cox regression analysis. 9 out of 10 DMGs revealed excellent performance as independent diagnostic predictors, including CLDN1, EPHX4, TCN1, ARHGAP20, LY6G6D, FAM150A, KCNJ12, KRT7 and STK33. Furthermore, STK33 and EPHX4 were found to be associated with Overall survival (OS). Conclusions: Our findings suggest that the identified MDGs could be potential biomarkers for diagnosis and prognosis of CRC.

scholarly journals Clinical Significance of Amyloid Precursor Protein in Patients with Testicular Germ Cell Tumor

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Yuta Yamada ◽  
Tetsuya Fujimura ◽  
Satoru Takahashi ◽  
Kenichi Takayama ◽  
Tomohiko Urano ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Germ Cell ◽  
Mrna Expression ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumor ◽  
Venous Invasion ◽  
Precursor Protein ◽  
Testicular Germ Cell ◽  
Aggressive Cancer

Introduction. The biological role of amyloid precursor protein (APP) is not well understood, especially in testicular germ cell tumors (TGCTs). Therefore, we aimed to investigate the immunoreactivity (IR) and expression of APP in TGCTs and evaluated its clinical relevance.Materials and Methods. We performed an analysis of immunohistochemistry and mRNA expression of APP in 64 testicular specimens and 21 snap-frozen samples obtained from 1985 to 2004. We then evaluated the association between APP expression and clinicopathological status in TGCTs.Results. Positive APP IR was observed in 9.8% (4/41) of seminomatous germ cell tumors (SGCTs) and 39.1% (9/23) of nonseminomatous germ cell tumors (NGCTs). NGCTs showed significantly more cases of positive IR(P=0.00870)and a higher mRNA expression level compared with those of SGCTs(P=0.0140). Positive APP IR was also significantly associated withα-fetoprotein (αFP) elevation(P=0.00870)and venous invasion(P=0.0414).Conclusion. We observed an elevated APP expression in TGCTs, especially in NGCTs. APP may be associated with a more aggressive cancer in TGCTs.

scholarly journals Pan-Cancer Analyses Reveal Genomic Features of FOXM1 Overexpression in Cancer

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 251 ◽  
Author(s):  
Carter Barger ◽  
Connor Branick ◽  
Linda Chee ◽  
Adam Karpf
Keyword(s):  
Human Cancer ◽  
Germ Cell Tumors ◽  
Tissue Expression ◽  
Genetic Alterations ◽  
The Cancer Genome Atlas ◽  
Testicular Germ Cell ◽  
Cyclin E1 ◽  
Basal Breast Cancer ◽  
Foxm1 Expression ◽  
Knockout Model

FOXM1 is frequently overexpressed in cancer, but this has not been studied in a comprehensive manner. We utilized genotype-tissue expression (GTEx) normal and The Cancer Genome Atlas (TCGA) tumor data to define FOXM1 expression, including its isoforms, and to determine the genetic alterations that promote FOXM1 expression in cancer. Additionally, we used human fallopian tube epithelial (FTE) cells to dissect the role of Retinoblastoma (Rb)-E2F and Cyclin E1 in FOXM1 regulation, and a novel human embryonic kidney cell (HEK293T) CRISPR FOXM1 knockout model to define isoform-specific transcriptional programs. FOXM1 expression, at the mRNA and protein level, was significantly elevated in tumors with FOXM1 amplification, p53 inactivation, and Rb-E2F deregulation. FOXM1 expression was remarkably high in testicular germ cell tumors (TGCT), high-grade serous ovarian cancer (HGSC), and basal breast cancer (BBC). FOXM1 expression in cancer was associated with genomic instability, as measured using aneuploidy signatures. FTE models confirmed a role for Rb-E2F signaling in FOXM1 regulation and in particular identified Cyclin E1 as a novel inducer of FOXM1 expression. Among the three FOXM1 isoforms, FOXM1c showed the highest expression in normal and tumor tissues and cancer cell lines. The CRISPR knockout model demonstrated that FOXM1b and FOXM1c are transcriptionally active, while FOXM1a is not. Finally, we were unable to confirm the existence of a FOXM1 auto-regulatory loop. This study provides significant and novel information regarding the frequency, causes, and consequences of elevated FOXM1 expression in human cancer.

scholarly journals The Role of DNA/Histone Modifying Enzymes and Chromatin Remodeling Complexes in Testicular Germ Cell Tumors

Cancers ◽  
2018 ◽  
Vol 11 (1) ◽  
pp. 6 ◽  
Author(s):  
João Lobo ◽  
Rui Henrique ◽  
Carmen Jerónimo
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
In Silico Analysis ◽  
Dna Methyltransferases ◽  
The Cancer Genome Atlas ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Chromatin Remodelers ◽  
Histone Modifying Enzymes

It is well established that cancer cells exhibit alterations in chromatin structure and accessibility. Indeed, the dysregulation of many protein-coding players with enzymatic activity (DNA and histone-modifying enzymes) and chromatin remodelers have been depicted in various tumor models in recent years. Still, little attention has been directed towards testicular germ cell tumors (TGCTs)—representing the most common neoplasm among young adult Caucasian men—with most studies focusing on exploring the role of DNA methyltransferases (DNMTs) and DNA demethylases (TETs). TGCTs represent a complex tumor model, associated with developmental and embryogenesis-related phenomena, and display seldom (cyto)genetic aberrations, leaving room for Epigenetics to explain such morphological and clinical diversity. Herein, we have summarized the major findings that were reported in literature regarding the dysregulation of DNA/histone-modifying enzymes and chromatin remodelers in TGCTs. Additionally, we performed in silico analysis of The Cancer Genome Atlas database to find the most relevant of those players in TGCTs. We concluded that several DNA/histone-modifying enzymes and chromatin remodelers may serve as biomarkers for subtyping, dictating prognosis and survival, and, possibly, for serving as targets of directed, less toxic therapies.

scholarly journals Refractory testicular germ cell tumors are highly sensitive to the second generation DNA methylation inhibitor guadecitabine

Oncotarget ◽  
2016 ◽  
Vol 8 (2) ◽  
pp. 2949-2959 ◽  
Author(s):  
Costantine Albany ◽  
Mary P. Hever-Jardine ◽  
Katherine M. von Herrmann ◽  
Christina Y. Yim ◽  
Janice Tam ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Germ Cell ◽  
Second Generation ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Highly Sensitive ◽  
Methylation Inhibitor ◽  
Dna Methylation Inhibitor

Serum Lactate Dehydrogenase Isoenzyme 1 and Relapse in Patients with Nonseminomatous Testicular Germ Cell Tumors Clinical Stage I

2001 ◽  
Vol 40 (4) ◽  
pp. 536-540 ◽  
Author(s):  
Finn Edler von Eyben ◽  
Ebbe Lindegaard Madsen ◽  
Ole Blaabjerg ◽  
Per Hyltoft Petersen ◽  
Hans von der Maase ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Germ Cell ◽  
Clinical Stage ◽  
Germ Cell Tumors ◽  
Serum Lactate ◽  
Stage I ◽  
Serum Lactate Dehydrogenase ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Dehydrogenase Isoenzyme
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