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 Role of microRNAs in mammalian spermatogenesis and testicular germ cell tumors

Reproduction ◽  
2015 ◽  
Vol 149 (3) ◽  
pp. R127-R137 ◽  
Author(s):  
Li Wang ◽  
Chen Xu
Keyword(s):  
Germ Cell ◽  
Expression Profiles ◽  
Regulation Of Gene Expression ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumors ◽  
Mirna Regulation ◽  
Testicular Germ Cell ◽  
Complex Process ◽  
Regulatory Functions

microRNAs (miRNAs) are a class of small endogenous RNAs, 19–25 nucleotides in size, which play a role in the regulation of gene expression at transcriptional and post-transcriptional levels. Spermatogenesis is a complex process through which spermatogonial stem cells (SSCs) proliferate and differentiate into mature spermatozoa. A large number of miRNAs are abundantly expressed in spermatogenic cells. Growing evidence supports the essential role of miRNA regulation in normal spermatogenesis and male fertility and cumulative research has shown that this form of regulation contributes to the etiology of testicular germ cell tumors (TGCTs). In this review, we addressed recent advancements of miRNA expression profiles in testis and focused on the regulatory functions of miRNA in the process of SSC renewal, spermatogonial mitosis, spermatocyte meiosis, spermiogenesis, and the occurrence of TGCTs.

scholarly journals Expression Profiles of PIWIL2 Short Isoforms Differ in Testicular Germ Cell Tumors of Various Differentiation Subtypes

PLoS ONE ◽  
2014 ◽  
Vol 9 (11) ◽  
pp. e112528 ◽  
Author(s):  
Ildar V. Gainetdinov ◽  
Yulia V. Skvortsova ◽  
Elena A. Stukacheva ◽  
Oksana S. Bychenko ◽  
Sofia A. Kondratieva ◽  
...  
Keyword(s):  
Germ Cell ◽  
Expression Profiles ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Short Isoforms

scholarly journals Integrated analysis of high-throughput sequencing data reveals the key role of LINC00467 in the invasion and metastasis of testicular germ cell tumors

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Hao Bo ◽  
Fang Zhu ◽  
Zhizhong Liu ◽  
Qi Deng ◽  
Guangmin Liu ◽  
...  
Keyword(s):  
Germ Cell ◽  
High Throughput Sequencing ◽  
Expression Profiles ◽  
Germ Cell Tumors ◽  
Differentially Expressed ◽  
Migration And Invasion ◽  
Integrated Analysis ◽  
Sequencing Data ◽  
Testicular Germ Cell

AbstractLong noncoding RNAs (lncRNAs) are involved in various physiological and pathological processes. However, the role of lncRNAs in testicular germ cell tumor (TGCT) has been rarely reported. Our purpose is to comprehensively survey the expression and function of lncRNAs in TGCT. In this study, we used RNA sequencing to construct the lncRNA expression profiles of 13 TGCT tissues and 4 paraneoplastic tissues to explore the function of lncRNAs in TGCT. The bioinformatics analysis showed that many lncRNAs are differentially expressed in TGCT. GO and KEGG enrichment analyses revealed that the differentially expressed lncRNAs participated in various biological processes associated with tumorigenesis in cis and trans manners. Further, we found that the expression of LINC00467 was positively correlated with the poor prognosis and pathological grade of TGCT using WGCNA analysis and GEPIA database data mining. In vitro experiments revealed that LNC00467 could promote the migration and invasion of TGCT cells by regulating the expression of AKT3 and influencing total AKT phosphorylation. Further analysis of TCGA data revealed that the expression was negatively correlated with the infiltration of immune cells and the response to PD1 immunotherapy. In summary, this study is the first to construct the expression profile of lncRNAs in TGCT. It is also the first study to identify the metastasis-promoting role of LNC00467, which can be used as a potential predictor of TGCT prognosis and immunotherapeutic response to provide a clinical reference for the treatment and diagnosis of TGCT metastasis.

scholarly journals RNA-Binding Proteins Play an Important Role in the Prognosis of Patients With Testicular Germ Cell Tumor

2021 ◽  
Vol 12 ◽  
Author(s):  
Liangyu Yao ◽  
Rong Cong ◽  
Chengjian Ji ◽  
Xiang Zhou ◽  
Jiaochen Luan ◽  
...  
Keyword(s):  
Germ Cell ◽  
Risk Score ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Expression Profiles ◽  
Germ Cell Tumors ◽  
Disease Free Survival ◽  
Testicular Germ Cell ◽  
Model Based

Testicular germ cell tumors (TGCTs) are common urological neoplasms in young adult males. The outcome of TGCT depends on pathologic type and tumor stage. RNA-binding proteins (RBPs) influence numerous cancers via post-transcriptional regulation. The prognostic importance of RBPs in TGCT has not been fully investigated. In this study, we set up a prognostic risk model of TGCT using six significantly differentially expressed RBPs, namely, TRMT61A, POLR2J, DIS3L2, IFIH1, IGHMBP2, and NPM2. The expression profiles were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression datasets. We observed by performing least absolute shrinkage and selection operator (LASSO) regression analyses that in the training cohort, the expression of six RBPs was correlated with disease-free survival in patients with TGCT. We assessed the specificity and sensitivity of 1-, 3-, 5-, and 10-year survival status prediction using receiver operating characteristic curve analysis and successfully validated using the test cohorts, the entire TCGA cohort, and Gene Expression Omnibus (GEO) datasets. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analyses were carried out to seek the possible signaling pathways related with risk score. We also examined the association between the model based on six RBPs and different clinical characteristics. A nomogram was established for TGCT recurrence prediction. Consensus clustering analysis was carried out to identify the clusters of TGCT with different clinical outcomes. Ultimately, external validations of the six-gene risk score were performed by using the GSE3218 and GSE10783 datasets downloaded from the GEO database. In general, our study constructed a prognostic model based on six RBPs, which could serve as independent risk factor in TGCT, especially in seminoma, and might have brilliant clinical application value.

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.

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 RNA-Binding Protein Dnd1 Promotes Breast Cancer Apoptosis by Stabilizing the Bim mRNA in a miR-221 Binding Site

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Feng Cheng ◽  
Ying Pan ◽  
Yi-Min Lu ◽  
Lei Zhu ◽  
Shuzheng Chen
Keyword(s):  
Breast Cancer ◽  
Germ Cell ◽  
Binding Site ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Expression Profiles ◽  
Germ Cell Tumors ◽  
Vital Role ◽  
The Cancer Genome Atlas ◽  
Mcf 7

RNA-binding proteins (RBPs) and miRNAs are capable of controlling processes in normal development and cancer. Both of them could determine RNA transcripts fate from synthesis to decay. One such RBP, Dead end (Dnd1), is essential for regulating germ-cell viability and suppresses the germ-cell tumors development, yet how it exerts its functions in breast cancer has remained unresolved. The level of Dnd1 was detected in 21 cancerous tissues paired with neighboring normal tissues by qRT-PCR. We further annotated TCGA (The Cancer Genome Atlas) mRNA expression profiles and found that the expression of Dnd1 and Bim is positively correlated (p=0.04). Patients with higher Dnd1 expression level had longer overall survival (p=0.0014) by KM Plotter tool. Dnd1 knockdown in MCF-7 cells decreased Bim expression levels and inhibited apoptosis. While knockdown of Dnd1 promoted the decay of Bim mRNA 3′UTR, the stability of Bim-5′UTR was not affected. In addition, mutation of miR-221-binding site in Bim-3′UTR canceled the effect of Dnd1 on Bim mRNA. Knockdown of Dnd1 in MCF-7 cells confirmed that Dnd1 antagonized miR-221-inhibitory effects on Bim expression. Overall, our findings indicate that Dnd1 facilitates apoptosis by increasing the expression of Bim via its competitive combining with miR-221 in Bim-3′UTR. The new function of Dnd1 may contribute to a vital role in breast cancer development.

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

Recent Advances in New Discovered Molecular Targets in Testicular Germ Cell Tumors

2018 ◽  
Vol 25 (5) ◽  
pp. 575-583 ◽  
Author(s):  
Paolo Chieffi
Keyword(s):  
Germ Cell ◽  
Primordial Germ Cells ◽  
Germ Cell Tumors ◽  
Molecular Targets ◽  
Testicular Germ Cell Tumor ◽  
Research Literature ◽  
Testicular Germ Cell ◽  
Solid Malignancy ◽  
Bibliographic Data ◽  
New Biomarkers

Background: Testicular germ cell tumor (TGCT) is the most common solid malignancy occurring in young men between 20 and 34 years of age, and its incidence has increased significantly over the last decades. TGCTs can be subdivided into seminoma and nonseminoma germ cell tumors (NSGCTs), which includes yolk sac tumor, choriocarcinoma, embryonal cell carcinoma, and teratoma. Seminomas and NSGCTs present significant differences in therapy, prognosis, and both show characteristics of the Primordial Germ Cells (PGCs). Methods: I undertook a search of bibliographic data from peer-reviewed research literature. Results: Seventy papers were included in the mini-review showing that a large number of new biomarkers have given further advantages to discriminate the different histotypes and could represent useful novel molecular targets for anticancer strategies. Conclusion: A deeper understanding of the pathogenesis of TGCTs is likely to significantly improve not only our knowledge on stem cells and oncogenesis but also the disease management with more selective tumor treatment.

Sign in / Sign up

Export Citation Format

Share Document