scholarly journals METTL3 May Regulate Testicular Germ Cell Tumors Through EMT and Immune Pathways

2020 ◽  
Vol 29 ◽  
pp. 096368972094665
Author(s):  
Yang Luo ◽  
Yuan Sun ◽  
Lei Li ◽  
Yuling Mao
Keyword(s):  
Molecular Markers ◽  
Germ Cell ◽  
Effective Treatment ◽  
Epithelial Mesenchymal Transition ◽  
Germ Cell Tumors ◽  
Migration And Invasion ◽  
Testicular Germ Cell Tumors ◽  
Migration Ability ◽  
Testicular Germ Cell ◽  
Mesenchymal Transition

Testicular germ cell tumors (TGCTs) are highly prevalent in young men aged 20–40 years and are one of the most common lethal solid tumors in men of this age. Due to the current unclear mechanism of tumor development, there is a lack of effective treatment, and therefore in-depth research of the molecular mechanism of the occurrence and development of TGCT and the search for suitable and effective therapeutic targets and molecular markers are of great significance for achieving effective treatment. METTL3 is a very important methylase, which has been implicated in the progression of many cancers, but the role of METTL3 in TGCT has not been fully elucidated. In this article, we found that METTL3 expression was significantly downregulated in TGCT tissues, and patients with low expression levels had lower overall survival and relapse-free survival rates. After overexpressing METTL3, cell proliferation, invasion, and migration ability significantly increased, while influencing the expression of epithelial–mesenchymal transition (EMT)-related proteins. In addition, we observed that the expression level of METTL3 positively correlated with molecular markers and infiltration level of CD8+ and CD4+ T cells and natural killer cells. In sum, our findings identified that METTL3 can be used as an independent prognostic marker in patients with TGCT. METTL3 participates in the proliferation, migration, and invasion of TGCT cells by regulating the expression of EMT-related genes and may also play a role in activating the tumor immune response in TGCT.

Molecular Markers in Testicular Germ Cell Tumors – Objects of Clinical Research or Close to Becoming Clinical Tools?

2001 ◽  
Vol 24 (2) ◽  
pp. 144-148 ◽  
Author(s):  
M. Schrader ◽  
R. Heicappell ◽  
M. Müller ◽  
H. Krause ◽  
B. Straub ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Clinical Research ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Clinical Tools

Brachyury, a driver of epithelial mesenchymal transition, as an independent prognostic factor in high-grade testicular germ cell tumors.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16039-e16039
Author(s):  
Flavio Mavignier Carcano ◽  
Filipe Pinto ◽  
Eduardo CA da Silva ◽  
Daniel Onofre Vidal ◽  
Cristovam Scapulatempo Neto ◽  
...  
Keyword(s):  
High Risk ◽  
Subcellular Localization ◽  
Germ Cell ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Germ Cell Tumors ◽  
Specific Marker ◽  
Nuclear Staining ◽  
Testicular Germ Cell ◽  
Mesenchymal Transition

e16039 Background: The T-box transcription factor Brachyury has been considered a cancer-specific marker and a novel oncotarget in solid tumors. Brachyury overexpression has been described in various cancers, being associated with epithelial-mesenchymal transition, metastasis and poor prognosis. However, its clinical association with testicular germ cell tumor (TGCT) is unknown. Methods: We analyzed the expression of Brachyury both at protein and transcript levels in a series of 96 TGCT samples and by in silico analysis, respectively. Additionally, we investigated the clinical significance of Brachyury in TGCT. Results: Brachyury protein showed to be over-represented in 89.6% (86/96) of TGCT cases with nuclear staining in 24% (23/96) of them. Microarray expression analysis in two independent cohorts of TGCTs showed similar results with increased levels of Brachyury in TGCTs and metastasis compared with normal testis. Clinically, Brachyury nuclear staining was statistically associated with event-free survival (p = 0.04) and overall survival (p = 0.01) in intermediate/high-risk TGCTs. Multivariate analysis showed that Brachyury nuclear subcellular localization was an independent predictor of poor prognosis (HR: 3.56, p = 0.06). Conclusions: These results indicate that Brachyury plays an oncogenic role in TGCTs and its subcellular localization in the nucleus is a potential novel biomarker of poor prognosis and an oncotarget for intermediate/high-risk TGCTs treatment.

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

Molecular Mechanisms of Resistance in Testicular Germ Cell Tumors - clinical Implications

2018 ◽  
Vol 18 (10) ◽  
pp. 967-978 ◽  
Author(s):  
Katarina Kalavska ◽  
Vincenza Conteduca ◽  
Ugo De Giorgi ◽  
Michal Mego
Keyword(s):  
Germ Cell ◽  
Molecular Mechanisms ◽  
Cisplatin Resistance ◽  
Apoptotic Cell ◽  
Germ Cell Tumors ◽  
Treatment Resistance ◽  
Experimental Models ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Repair Capacity

Testicular germ cell tumors (TGCTs) represent the most common malignancy in men aged 15-35. Due to these tumors’ biological and clinical characteristics, they can serve as an appropriate system for studying molecular mechanisms associated with cisplatin-based treatment resistance. This review describes treatment resistance from clinical and molecular viewpoints. Cisplatin resistance is determined by various biological mechanisms, including the modulation of the DNA repair capacity of cancer cells, alterations to apoptotic cell death pathways, deregulation of gene expression pathways, epigenetic alterations and insufficient DNA binding. Moreover, this review describes TGCTs as a model system that enables the study of the cellular features of cancer stem cells in metastatic process and describes experimental models that can be used to study treatment resistance in TGCTs. All of the abovementioned aspects may help to elucidate the molecular mechanisms underlying cisplatin resistance and may help to identify promising new therapeutic targets.

scholarly journals Teratomatous Elements in Orchiectomy Specimens Are Associated with a Reduced Relapse-Free Survival in Metastasized Testicular Germ Cell Tumors

2021 ◽  
pp. 1-7
Author(s):  
Pia Paffenholz ◽  
Tim Nestler ◽  
Yasmine Maatoug ◽  
Melanie von Brandenstein ◽  
Barbara Köditz ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
Retroperitoneal Lymph Node Dissection ◽  
Advanced Tumor Stage ◽  
Testicular Germ Cell Tumors ◽  
Relapse Free Survival ◽  
Testicular Germ Cell ◽  
Free Survival ◽  
Advanced Tumor ◽  
The Impact

<b><i>Introduction:</i></b> The impact of teratomatous elements in orchiectomy specimens of metastasized testicular germ cell tumors (TGCT) regarding oncological outcome is still unclear. <b><i>Methods:</i></b> We performed a retrospective analysis including 146 patients with metastasized TGCT analysing patient characteristics. <b><i>Results:</i></b> Twenty-six (18%) of all patients showed teratomatous elements in the orchiectomy specimens. TGCT with teratomatous elements showed a significantly higher frequency of clinical-stage 2C-3 disease (73 vs. 49%, <i>p</i> = 0.031), visceral metastases (58 vs. 32%, <i>p</i> = 0.015), and poor prognosis (<i>p</i> = 0.011) than TGCT without teratomatous elements. Teratoma-containing TGCT revealed a significantly higher rate of post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND, 54 vs. 32%, <i>p</i> = 0.041), with teratomatous elements being more often present in the PC-RPLND specimens (43 vs. 11%, <i>p</i> = 0.020) than nonteratoma-containing primaries. In the Kaplan-Meier estimates, the presence of teratomatous elements in orchiectomy specimens was associated with a significantly reduced relapse-free survival (RFS) (<i>p</i> = 0.049) during a median follow-up of 36 months (10–115.5). <b><i>Conclusions:</i></b> The presence of teratomatous elements in orchiectomy specimens is associated with an advanced tumor stage, worse treatment response as well as a reduced RFS in metastasized TGCT. Consequently, the presence of teratomatous elements might act as a reliable stratification tool for treatment decision in TGCT patients.

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