scholarly journals MiR-371a-3p Serum Levels Are Increased in Recurrence of Testicular Germ Cell Tumor Patients

2018 ◽  
Vol 19 (10) ◽  
pp. 3130 ◽  
Author(s):  
Angelika Terbuch ◽  
Jan Adiprasito ◽  
Verena Stiegelbauer ◽  
Maximilian Seles ◽  
Christiane Klec ◽  
...  
Keyword(s):  
Germ Cell ◽  
Tumor Markers ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumor ◽  
Serum Levels ◽  
Disease Recurrence ◽  
Salvage Chemotherapy ◽  
Disease Relapse ◽  
Serum Samples ◽  
Testicular Germ Cell

Metastatic testicular germ cell tumors (TGCTs) are a potentially curable disease by administration of risk-adapted cytotoxic chemotherapy. Nevertheless, a disease-relapse after curative chemotherapy needs more intensive salvage chemotherapy and significantly worsens the prognosis of TGCT patients. Circulating tumor markers (β-subunit of human chorionic gonadotropin (β-HCG), alpha-Fetoprotein (AFP), and Lactate Dehydrogenase (LDH)) are frequently used for monitoring disease recurrence in TGCT patients, though they lack diagnostic sensitivity and specificity. Increasing evidence suggests that serum levels of stem cell-associated microRNAs (miR-371a-3p and miR-302/367 cluster) are outperforming the traditional tumor markers in terms of sensitivity to detect newly diagnosed TGCT patients. The aim of this study was to investigate whether these miRNAs are also informative in detection of disease recurrence in TGCT patients after curative first line therapy. For this purpose, we measured the serum levels of miR-371a-3p and miR-367 in 52 samples of ten TGCT patients at different time points during disease relapse and during salvage chemotherapy. In our study, miR-371a-3p levels in serum samples with proven disease recurrence were 13.65 fold higher than levels from the same patients without evidence of disease (p = 0.014). In contrast, miR-367 levels were not different in these patient groups (p = 0.985). In conclusion, miR-371a-3p is a sensitive and potentially novel biomarker for detecting disease relapse in TGCT patients. This promising biomarker should be investigated in further large prospective trials.

scholarly journals Combining Hypermethylated RASSF1A Detection Using ddPCR with miR-371a-3p Testing: An Improved Panel of Liquid Biopsy Biomarkers for Testicular Germ Cell Tumor Patients

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5228
Author(s):  
João Lobo ◽  
Lieke M. J. van Zogchel ◽  
Mohammed G. Nuru ◽  
Ad J. M. Gillis ◽  
C. Ellen van der Schoot ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumor ◽  
Residual Disease ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumor ◽  
Cell Tumor ◽  
Adult Males ◽  
Serum Samples ◽  
Liquid Biopsies ◽  
Testicular Germ Cell

The classical serum tumor markers used routinely in the management of testicular germ cell tumor (TGCT) patients—alpha fetoprotein (AFP) and human chorionic gonadotropin (HCG)—show important limitations. miR-371a-3p is the most recent promising biomarker for TGCTs, but it is not sufficiently informative for detection of teratoma, which is therapeutically relevant. We aimed to test the feasibility of hypermethylated RASSF1A (RASSF1AM) detected in circulating cell-free DNA as a non-invasive diagnostic marker of testicular germ cell tumors, combined with miR-371a-3p. A total of 109 serum samples of patients and 29 sera of healthy young adult males were included, along with representative cell lines and tumor tissue samples. We describe a novel droplet digital polymerase chain reaction (ddPCR) method for quantitatively assessing RASSF1AM in liquid biopsies. Both miR-371a-3p (sensitivity = 85.7%) and RASSF1AM (sensitivity = 86.7%) outperformed the combination of AFP and HCG (sensitivity = 65.5%) for TGCT diagnosis. RASSF1AM detected 88% of teratomas. In this representative cohort, 14 cases were negative for miR-371a-3p, all of which were detected by RASSF1AM, resulting in a combined sensitivity of 100%. We have described a highly sensitive and specific panel of biomarkers for TGCT patients, to be validated in the context of patient follow-up and detection of minimal residual disease.

scholarly journals The Past and Future of Biomarkers in Testicular Germ Cell Tumors

2020 ◽  
Vol 1 (1) ◽  
pp. 77-84
Author(s):  
Aditya Bagrodia ◽  
Siamak Daneshmand ◽  
Liang Cheng ◽  
James Amatruda ◽  
Matthew Murray ◽  
...  
Keyword(s):  
Germ Cell ◽  
Tumor Markers ◽  
Critical Role ◽  
Elevated Serum ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumor ◽  
Next Generation ◽  
Testicular Germ Cell ◽  
Circulating Micrornas ◽  
Serum Tumor Markers

Testicular germ cell tumor (GCT) is the most common malignancy in 18- to 40-year-old men. Unlike most other cancers, GCT is frequently curable even when metastatic. These tumors can be classified histologically into seminoma and non-seminoma, which determines treatment. Therefore, successful treatment requires accurate diagnosis, classification, and monitoring. Serum tumor markers, including lactate dehydrogenase, α-fetoprotein, and β-human chorionic gonadotropin, aid in the classification and staging of GCTs. These markers therefore play a critical role in the decision-making process when managing GCT patients. However, there exist many scenarios in which these markers fail to perform adequately. This is particularly true in the case of seminoma, where only 10% to 15% will have elevated serum tumor markers. Non-specific elevation of these markers is also a common occurrence, complicating the interpretation of borderline positive results, particularly in follow-up. To bridge this gap in performance, next generation biomarkers are being investigated. In this review, we consider the role of conventional serum tumor markers in GCT management and discuss recent advances in the next generation of biomarkers, with a focus on circulating microRNAs. We discuss the value that circulating microRNAs could bring as an addition to currently used markers, as well as potential weaknesses, in GCT management.

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.

scholarly journals Predictors of Venous Thromboembolism in Patients With Testicular Germ Cell Tumors: A Retrospective Study

2021 ◽  
Vol 27 ◽  
pp. 107602962110247
Author(s):  
Hikmat Abdel-Razeq ◽  
Faris Tamimi ◽  
Rashid Abdel-Razeq ◽  
Samer Salah ◽  
Zaid Omari ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Germ Cell ◽  
Metastatic Disease ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumor ◽  
Tumor Burden ◽  
Testicular Tumors ◽  
Testicular Germ Cell ◽  
Node Positive ◽  
Age Range

Malignancy, including testicular tumors, significantly increases the risk of venous thromboembolism (VTE). In this study, we search for predictors that may help identify subgroups of patients at higher risk of VTE. Patients with confirmed diagnosis of testicular germ cell tumor and proven VTE were identified. Clinical and pathological features possibly associated with VTE were reviewed. A total of 322 patients, median age (range) 31 (18-76) years were identified. Tumors were mostly non-seminoma (n = 194, 60.2%), node-positive (n = 130, 40.4%) and 58 (18.0%) had metastatic disease at diagnosis. Venous thromboembolism were confirmed in 27 (8.4%) patients; however, rates were significantly higher ( P < 0.001) in patients with node-positive (18.5%), metastatic disease (22.4%), and those with high lactate dehydrogenase (LDH) (21.3%). Rates were also significantly higher among those who received multiple lines of chemotherapy (27.5%) compared to those who received one line (13.8%) or none (<1.0%), P < 0.001. Patients with testicular tumors and high tumor burden, including nodal involvement, high LDH or metastatic disease, and those treated with multiple lines of chemotherapy have significantly higher rates of VTE.

scholarly journals Differential methylation EPIC analysis discloses cisplatin-resistance related hypermethylation and tumor-specific heterogeneity within matched primary and metastatic testicular germ cell tumor patient tissue samples

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
João Lobo ◽  
Vera Constâncio ◽  
Pedro Leite-Silva ◽  
Rita Guimarães ◽  
Mariana Cantante ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumor ◽  
Complete Response ◽  
Differential Analysis ◽  
Testicular Germ Cell ◽  
Tissue Samples ◽  
Tumor Patient ◽  
Resistant Disease ◽  
Response To Chemotherapy

AbstractTesticular germ cell tumors (TGCTs) are among the most common solid malignancies in young-adult men, and currently most mortality is due to metastatic disease and emergence of resistance to cisplatin. There is some evidence that increased methylation is one mechanism behind this resistance, stemming from individual studies, but approaches based on matched primary and metastatic patient samples are lacking. Herein, we provide an EPIC array-based study of matched primary and metastatic TGCT samples. Histology was the major determinant of overall methylation pattern, but some clustering of samples related to response to cisplatin was observed. Further differential analysis of patients with the same histological subtype (embryonal carcinoma) disclosed a remarkable increase in net methylation levels (at both promoter and CpG site level) in the patient with cisplatin-resistant disease and poor outcome compared to the patient with complete response to chemotherapy. This further confirms the recent results of another study performed on isogenic clones of sensitive and resistant TGCT cell lines. Differentially methylated promoters among groups of samples were mostly not shared, disclosing heterogeneity in patient tissue samples. Finally, gene ontology analysis of cisplatin-resistant samples indicated enrichment of differentially hypermethylated promoters on pathways related to regulation of immune microenvironment, and enrichment of differentially hypomethylated promoters on pathways related to DNA/chromatin binding and regulation. This data supports not only the use of hypomethylating agents for targeting cisplatin-resistant disease, but also their use in combination with immunotherapies and chromatin remodelers.

Testicular Germ Cell Tumor and down Syndrome

2000 ◽  
Vol 86 (5) ◽  
pp. 431-433 ◽  
Author(s):  
María José Villanueva ◽  
Fátima Navarro ◽  
Antonio Sánchez ◽  
Mariano Provencio ◽  
Félix Bonilla ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Germ Cell ◽  
Germ Cell Tumor ◽  
Medical Literature ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumor ◽  
Cell Tumor ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
English Medical Literature

The association between Down syndrome and testicular germ cell tumors may be more frequent than expected according to chance, but few reports have focused on this excess. We report two cases of this association and review the English medical literature.

Evidence for Altered Hypothalamic-Hypophyseal-Gonadal Axis in Untreated Patients with Testicular Germ-Cell Tumor

1989 ◽  
Vol 75 (5) ◽  
pp. 505-509
Author(s):  
Sergio Crispino ◽  
Gabriele Tancini ◽  
Sandro Barni ◽  
Paolo Lissoni
Keyword(s):  
Testicular Cancer ◽  
Germ Cell ◽  
Germ Cell Tumor ◽  
Venous Blood ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumor ◽  
Cell Tumor ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Significant Difference

To investigate the function of the hypothalamic-hypophyseal-gonadal axis in testicular germ cell tumors, we evaluated gonadotropin responses to gonadotropin-releasing hormone (GnRH) in 12 untreated patients with testicular cancer (5 seminomas and 7 non-seminomas). GnRH was given i.v. at a dose of 100 μg as a bolus, and venous blood samples were collected at 0, 20, 60, and 120 min. As controls, 14 healthy males were studied. Basal levels of testosterone, estradiol and prolactin were also detected in each patient. Hormonal serum concentrations were measured by the radioimmunoassay. Mean basal testosterone, estradiol and prolactin levels were not significantly different from those of controls. Patients had a lower FSH and LH peak after GnRH than controls, without, however, any significant difference. As regards histology, nonseminoma patients lacked an FSH response to GnRH and had statistically lower mean peak levels than controls. Moreover, non-seminoma patients had statistically lower mean peak values of LH after GnRH than controls. These data show that patients with testicular germ cell tumor, and more particularly those with non-seminomas, have an altered function of the hypothalamic-hypophyseal-gonadal axis, which is already present prior to therapy. Further studies, particularly in stage I patients treated only with orchiectomy, should be performed to confirm and better define the Physiopathologic significance of the altered hypothalamic-hypophyseal-gonadal axis in testicular cancer and to clarify the alteration of fertility, which is frequently present before treatment.

scholarly journals Evaluation of Circulating miRNA Biomarkers of Testicular Germ Cell Tumors during Therapy and Follow-up―A Copenhagen Experience

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 759
Author(s):  
Nina Mørup ◽  
Ewa Rajpert-De Meyts ◽  
Anders Juul ◽  
Gedske Daugaard ◽  
Kristian Almstrup
Keyword(s):  
Germ Cell ◽  
Tumor Markers ◽  
Germ Cell Tumors ◽  
Primary Diagnosis ◽  
University Hospital ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Circulating Mirna ◽  
Serum Tumor Markers

New microRNA-based serum biomarkers (miRNA-367-3p, -371a-3p, -372-3p, and -373-3p) have shown great potential for the detection of testicular germ cell tumors (TGCTs), but few studies have investigated the clinical utility and performance of these tests in treatment monitoring. In this study, circulating miRNA levels were measured, together with serum tumor markers alpha-fetoprotein (AFP), β-subunit of human chorionic gonadotropin (β-HCG) and lactate dehydrogenase (LDH) in 406 consecutive blood samples obtained during the treatment and follow-up of 52 TGCT patients at the Copenhagen University Hospital. After testing three different methods of RNA isolation from peripheral blood and PCR quantification in a subset of samples (n = 15), the best performing setup of targeted isolation of miRNAs inside and outside exosomes was selected to analyze all samples. At primary diagnosis, the miRNAs significantly outperformed the serum tumor markers, with a sensitivity and specificity of 78% and 100% (based on 40 patients), respectively. The picture was not as clear when patient trajectories were investigated, with both positive and negative signals for miRNAs and serum tumor markers. To establish whether measuring miRNAs adds value beyond the primary diagnosis, large prospective clinical trials comparing miRNAs and classical tumor markers during the treatment and follow-up of TGCT patients are needed.

Is measuring serum levels of microRNA miR-371a-3p superior to the classical biomarkers of testicular germ cell tumors?

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 376-376 ◽  
Author(s):  
Klaus-Peter Dieckmann ◽  
Meike Spiekermann ◽  
Christian G Ruf ◽  
Karin Oechsle ◽  
Gazanfer Belge
Keyword(s):  
Germ Cell ◽  
Large Scale ◽  
Quantitative Polymerase Chain Reaction ◽  
Germ Cell Tumors ◽  
Internal Standard ◽  
Serum Levels ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Multicentric Study ◽  
Stage 1

376 Background: There is need for more serum biomarkers of testicular germ cell tumors (GCTs) because the management of GCT is largely based on marker monitoring but only 60% of patients express the classical markers AFP and beta HCG. We measured serum levels of microRNA miR-371a-3p (miR-371) in GCT patients with the aim of establishing a new biomarker. Methods: Serum samples of 130 consecutive patients with GCT (75 seminoma, 55 nonseminoma; 90 clinical stage 1, 40 higher stages) were examined for miR-371a-3p before and after treatment. 105 young males with nonmalignant testicular diseases and 10 patients with non-GCT testis tumors served as controls. Serum levels of miR-371a-3p were measured by quantitative polymerase chain reaction with quantification in relation to miR-20a as internal standard. Measurements were correlated with clinical data, analysis involved descriptive statistical methods. Results: Over 90% of all patients had higher serum levels of miR-371a-3p than controls. After treatment, all elevated levels decreased to the normal range. All metastasized patients had significantly higher mean levels than stage 1 patients, serum levels appear to correlate with tumor bulk. Upon chemotherapy levels decreased with each cycle of therapy. After orchiectomy in stage 1 cases, serum levels dropped by 95% within 24 hours. Nonseminomas had higher mean levels than seminoma. Teratoma does not express miR-371a-3p. The levels remained low during follow-up. Conclusions: Serum levels of microRNA miR-371a-3p appear to comprise of all attributes of a valuable serum biomarker of germ cell tumors. This marker is also expressed in seminoma and it apparently outperforms the classical markers. Evaluation in a large scale multicentric study is warranted.

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