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Molecular Biology of Testicular Germ Cell Tumours
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Molecular Biology of Testicular Germ Cell Tumours

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 7310

Special Issue Editor

Dr. Miroslav Chovanec

E-Mail Website
Guest Editor
Department of Genetics, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Dúbravská cesta 9, 845 05 Bratislava, Slovakia
Interests: DNA damage; DNA repair; cancer; biomarker; targeted therapy; treatment personalization
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Testicular germ cell tumours (TGCTs) represent the most chemosensitive solid malignancy; up to 70–80% of patients with metastatic disease can be cured with first-line standard-dose cisplatin (CDDP)-based chemotherapy. Nevertheless, 20–30% of patients relapse or do not respond to therapy. About 20–25% of relapsed patients may be cured with salvage conventional or high dose chemotherapy. However, patients who fail to be cured with salvage chemotherapy have a poor prognosis. Therefore, there is an urgent need to understand the difference between good and poor prognosis in patients at a molecular level and to use these findings, after their clinical validation, to effeviently and accurately stratify TGCT patients.

Authors are warmly invited to submit original research and review articles to this Special Issue which addresses the latest progress and current understanding of molecular mechanisms driving TGCT development and progression. Mechanisms responsible for the high curability of TGCTs and their underlying disease refractoriness and relapse are also important topics of this Special Issue. As testes are characterized by an immunologically privileged status, deeper insights into the uniqueness of TGCT infiltration by immune cells, TGCT microenvironment changes due to immune and inflammation factors, and the role of immune cells in promoting angiogenesis, tumour growth, invasion and metastasis, represent another area of interest in this issue. Submissions that address OMICS data produced by the high-throughput methods and their subsequent clinical validation in terms of their prognostic value will be highly appreciated in this Special Issue.

Dr. Miroslav Chovanec
Guest Editor

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Keywords

  • TGCTs
  • biomarkers
  • high-throughput methodologies
  • OMICS data
  • TGCT cell lines
  • clinical validation
  • therapy response
  • TGCT microenvironment
  • immune environment in TGCTs
  • TGCT burden
  • molecular stratification of TGCT patients
  • TGCT burnout

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Published Papers (4 papers)

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Research

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17 pages, 3023 KiB  
Article
SPTBN1 Mediates the Cytoplasmic Constraint of PTTG1, Impairing Its Oncogenic Activity in Human Seminoma
by Emanuela Teveroni, Fiorella Di Nicuolo, Edoardo Vergani, Alessandro Oliva, Emanuele Pierpaolo Vodola, Giada Bianchetti, Giuseppe Maulucci, Marco De Spirito, Tonia Cenci, Francesco Pierconti, Gaetano Gulino, Federica Iavarone, Andrea Urbani, Domenico Milardi, Alfredo Pontecorvi and Francesca Mancini
Int. J. Mol. Sci. 2023, 24(23), 16891; https://doi.org/10.3390/ijms242316891 - 29 Nov 2023
Viewed by 1262
Abstract
Seminoma is the most common testicular cancer. Pituitary tumor-transforming gene 1 (PTTG1) is a securin showing oncogenic activity in several tumors. We previously demonstrated that nuclear PTTG1 promotes seminoma tumor invasion through its transcriptional activity on matrix metalloproteinase 2 (MMP-2) and [...] Read more.
Seminoma is the most common testicular cancer. Pituitary tumor-transforming gene 1 (PTTG1) is a securin showing oncogenic activity in several tumors. We previously demonstrated that nuclear PTTG1 promotes seminoma tumor invasion through its transcriptional activity on matrix metalloproteinase 2 (MMP-2) and E-cadherin (CDH1). We wondered if specific interactors could affect its subcellular distribution. To this aim, we investigated the PTTG1 interactome in seminoma cell lines showing different PTTG1 nuclear levels correlated with invasive properties. A proteomic approach upon PTTG1 immunoprecipitation uncovered new specific securin interactors. Western blot, confocal microscopy, cytoplasmic/nuclear fractionation, sphere-forming assay, and Atlas database interrogation were performed to validate the proteomic results and to investigate the interplay between PTTG1 and newly uncovered partners. We observed that spectrin beta-chain (SPTBN1) and PTTG1 were cofactors, with SPTBN1 anchoring the securin in the cytoplasm. SPTBN1 downregulation determined PTTG1 nuclear translocation, promoting its invasive capability. Moreover, a PTTG1 deletion mutant lacking SPTBN1 binding was strongly localized in the nucleus. The Atlas database revealed that seminomas that contained higher nuclear PTTG1 levels showed significantly lower SPTBN1 levels in comparison to non-seminomas. In human seminoma specimens, we found a strong PTTG1/SPTBN1 colocalization that decreases in areas with nuclear PTTG1 distribution. Overall, these results suggest that SPTBN1, along with PTTG1, is a potential prognostic factor useful in the clinical management of seminoma. Full article
(This article belongs to the Special Issue Molecular Biology of Testicular Germ Cell Tumours)
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Review

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12 pages, 259 KiB  
Review
MicroRNAs in Testicular Germ Cell Tumors: The Teratoma Challenge
by Nuphat Yodkhunnatham, Kshitij Pandit, Dhruv Puri, Kit L. Yuen and Aditya Bagrodia
Int. J. Mol. Sci. 2024, 25(4), 2156; https://doi.org/10.3390/ijms25042156 - 10 Feb 2024
Cited by 4 | Viewed by 1751
Abstract
Testicular germ cell tumors (TGCTs) are relatively common in young men, making accurate diagnosis and prognosis assessment essential. MicroRNAs (miRNAs), including microRNA-371a-3p (miR-371a-3p), have shown promise as biomarkers for TGCTs. This review discusses the recent advancements in the use of miRNA biomarkers in [...] Read more.
Testicular germ cell tumors (TGCTs) are relatively common in young men, making accurate diagnosis and prognosis assessment essential. MicroRNAs (miRNAs), including microRNA-371a-3p (miR-371a-3p), have shown promise as biomarkers for TGCTs. This review discusses the recent advancements in the use of miRNA biomarkers in TGCTs, with a focus on the challenges surrounding the noninvasive detection of teratomas. Circulating miR-371a-3p, which is expressed in undifferentiated TGCTs but not in teratomas, is a promising biomarker for TGCTs. Its detection in serum, plasma, and, potentially, cystic fluid could be useful for TGCT diagnosis, surveillance, and monitoring of therapeutic response. Other miRNAs, such as miR-375-3p and miR-375-5p, have been investigated to differentiate between TGCT subtypes (teratoma, necrosis/fibrosis, and viable tumors), which can aid in treatment decisions. However, a reliable marker for teratoma has yet to be identified. The clinical applications of miRNA biomarkers could spare patients from unnecessary surgeries and allow for more personalized therapeutic approaches. Particularly in patients with residual masses larger than 1 cm following chemotherapy, it is critical to differentiate between viable tumors, teratomas, and necrosis/fibrosis. Teratomas, which mimic somatic tissues, present a challenge in differentiation and require a comprehensive diagnostic approach. The combination of miR-371 and miR-375 shows potential in enhancing diagnostic precision, aiding in distinguishing between teratomas, viable tumors, and necrosis. The implementation of miRNA biomarkers in TGCT care could improve patient outcomes, reduce overtreatment, and facilitate personalized therapeutic strategies. However, a reliable marker for teratoma is still lacking. Future research should focus on the clinical validation and standardization of these biomarkers to fully realize their potential. Full article
(This article belongs to the Special Issue Molecular Biology of Testicular Germ Cell Tumours)
13 pages, 960 KiB  
Review
Biomarkers for Salvage Therapy in Testicular Germ Cell Tumors
by Milena Urbini, Sara Bleve, Giuseppe Schepisi, Cecilia Menna, Giorgia Gurioli, Caterina Gianni and Ugo De Giorgi
Int. J. Mol. Sci. 2023, 24(23), 16872; https://doi.org/10.3390/ijms242316872 - 28 Nov 2023
Cited by 3 | Viewed by 1504
Abstract
The outcome of metastatic testicular germ cell tumor patients has been dramatically improved by cisplatin-based chemotherapy combinations. However, up to 30% of patients with advanced disease relapse after first-line therapy and require salvage regimens, which include treatments with conventional-dose chemotherapy or high-dose chemotherapy [...] Read more.
The outcome of metastatic testicular germ cell tumor patients has been dramatically improved by cisplatin-based chemotherapy combinations. However, up to 30% of patients with advanced disease relapse after first-line therapy and require salvage regimens, which include treatments with conventional-dose chemotherapy or high-dose chemotherapy with autologous stem cell transplantation. For these patients, prognosis estimation represents an essential step in the choice of medical treatment but still remains a complex challenge. The available histological, clinical, and biochemical parameters attempt to define the prognosis, but they do not reflect the tumor’s molecular and pathological features and do not predict who will exhibit resistance to the several treatments. Molecular selection of patients and validated biomarkers are highly needed in order to improve current risk stratification and identify novel therapeutic approaches for patients with recurrent disease. Biomolecular biomarkers, including microRNAs, gene expression profiles, and immune-related biomarkers are currently under investigation in testicular germ cell tumors and could potentially hold a prominent place in the future treatment selection and prognostication of these tumors. The aim of this review is to summarize current scientific data regarding prognostic and predictive biomarkers for salvage therapy in testicular germ cell tumors. Full article
(This article belongs to the Special Issue Molecular Biology of Testicular Germ Cell Tumours)
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26 pages, 4869 KiB  
Review
Once upon a Testis: The Tale of Cyclic Nucleotide Phosphodiesterase in Testicular Cancers
by Federica Campolo, Maria Rita Assenza, Mary Anna Venneri and Federica Barbagallo
Int. J. Mol. Sci. 2023, 24(8), 7617; https://doi.org/10.3390/ijms24087617 - 20 Apr 2023
Viewed by 2280
Abstract
Phosphodiesterases are key regulators that fine tune the intracellular levels of cyclic nucleotides, given their ability to hydrolyze cAMP and cGMP. They are critical regulators of cAMP/cGMP-mediated signaling pathways, modulating their downstream biological effects such as gene expression, cell proliferation, cell-cycle regulation but [...] Read more.
Phosphodiesterases are key regulators that fine tune the intracellular levels of cyclic nucleotides, given their ability to hydrolyze cAMP and cGMP. They are critical regulators of cAMP/cGMP-mediated signaling pathways, modulating their downstream biological effects such as gene expression, cell proliferation, cell-cycle regulation but also inflammation and metabolic function. Recently, mutations in PDE genes have been identified and linked to human genetic diseases and PDEs have been demonstrated to play a potential role in predisposition to several tumors, especially in cAMP-sensitive tissues. This review summarizes the current knowledge and most relevant findings regarding the expression and regulation of PDE families in the testis focusing on PDEs role in testicular cancer development. Full article
(This article belongs to the Special Issue Molecular Biology of Testicular Germ Cell Tumours)
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