Discriminating metastasised from non-metastasised seminoma based on transcriptional changes in primary tumours using NGS

Ruf, Christian; Schmelz, Hans-Ulrich; Port, Matthias; Wagner, Walter; Matthies, Cord; Müller‐Myhsok, Bertram; Meineke, Viktor; Abend, Michael

doi:10.1038/bjc.2014.134

Cited by 9 publications

(7 citation statements)

References 25 publications

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“…Within these, we found no difference between synchronously and metachronously metastatic tumours, suggesting a common role of these miRNAs in metastasis irrespective of the time of diagnosis. These results are consistent with the findings of others that report almost indistinguishable results for the transcriptional levels between synchronously and metachronously metastatic SGCT 16,17 . In summary, our results indicate that non‐metastatic and metastatic SGCT can be distinguished by specific miRNA expression patterns.…”

Section: Discussionsupporting

confidence: 93%

“…A two-miRNA combination (eg miR-29c + Enst00000387347; miR-29a + Enst00000387347) was defined that discriminated metastatic from non-metastatic tumours. 17 Consistent to our work miR-29c was expressed at significantly different levels in metastatic compared to non-metastatic tumours. Unfortunately, Ruf et al did not further describe if −3p or −5p was examined.…”

Section: Discussionsupporting

confidence: 90%

“…These results are consistent with the findings of others that report almost indistinguishable results for the transcriptional levels between synchronously and metachronously metastatic SGCT. 16,17 In summary, our results indicate that non-metastatic and metastatic SGCT can be distinguished by specific miRNA expression patterns. Furthermore, they did not validate their results by qRT-PCR.…”

Section: Discussionmentioning

confidence: 61%

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The metastatic potential of seminomatous germ cell tumours is associated with a specific microRNA pattern

et al. 2020

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Background Seminomatous germ cell tumours (SGCT) are the most frequent malignancy in young men. Reliable prognostic biomarkers for the prediction of metastasis at diagnosis and the risk of relapse in clinical stage I (CSI) are lacking. Adjuvant therapies carry a risk of overtreatment, whereas salvage therapies have a risk of high toxicities. Thus, the identification of reliable prognostic biomarkers is highly desirable to identify patients who will benefit from early adjuvant treatment. MicroRNAs (miRNAs) regulate tumour development and progression, and their potential as biomarkers has already been proven in a variety of malignancies. Objectives The aim of our study was to define a specific miRNA expression pattern that discriminates metastatic from non‐metastatic primary SGCT. Materials and methods Total RNA was isolated from 24 formalin‐fixed paraffin‐embedded (FFPE) primary SGCT tumours (10 non‐metastatic, five metachronously and nine synchronously metastatic) and from 10 normal testicular tissue samples. Microarray analysis was performed for global miRNA expression profiling. The results were validated by quantitative real‐time polymerase chain reaction (qRT‐PCR). Statistical analysis was performed using SPSS. Results Microarray analyses revealed a specific miRNA pattern that distinguishes metastatic from non‐metastatic SGCT. Sixty‐three miRNAs were differentially expressed in metastatic compared to non‐metastatic tumours (P < .01). Microarray results were confirmed by qRT‐PCR for three out of five selected miRNAs (miR‐29c‐5p, miR‐506‐3p and miR‐371a‐5p; P < .05). All five miRNAs (miR‐29c‐5p, miR‐506‐3p, miR‐1307‐5p, miR‐371a‐5p and miR‐371a‐3p) showed differential expression between tumour and normal tissues (P < .05). Conclusion Metastatic primary SGCTs are characterized by a specific miRNA expression pattern. Therefore, specific miRNAs could represent a new tool to predict the metastatic potential in SGCT patients.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 61%

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The metastatic potential of seminomatous germ cell tumours is associated with a specific microRNA pattern

et al. 2020

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“…Specific genes that were found to have a significant association with metastatic seminoma were dopamine receptor D1 (DRD1) and family with sequence similarity 71 (FAM71F2), and when combined into a single model had 87% concordance. In addition small RNA copy number changes may be able to even better discriminate between metastatic and nonmetastatic disease . We are currently embarking on such a study in a smaller cohort of patients who have available tumor specimens for testing.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of a prognostic model for risk of relapse in stage I seminoma surveillance

et al. 2014

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A prognostic model for relapse risk in stage I seminoma managed by surveillance after orchiectomy has been developed but has not been independently validated. Individual data on 685 stage I seminoma surveillance patients managed between 1998 and 2005 at three cancer centers were retrospectively analyzed. Variables including age and pathology of the primary tumor: small vessel invasion, tumor size, and invasion of rete testis were analyzed. Specifically median tumor size and rete testis invasion was tested to evaluate the performance of the published model. Median follow-up was 3.85 years (0.1–10.29), 88 patients relapsed and 5-year relapse-free rate was 85%. In univariate analysis, median tumor size (<3 cm vs. ≥3 cm) was associated with increased risk of relapse but rete testis invasion was not, nor was age and small vessel invasion. In multivariable analysis, tumor size above median (cutpoint of 3 cm) was a predictor for relapse, HR 1.87 (95% CI 1.15, 3.06), whereas rete testis invasion HR 1.36, (95% CI 0.81, 2.28) was not statistically significant. The 3-year relapse risk based on the primary tumor size alone increased from 9% for 1 cm primary tumor to 26% for 8 cm tumor. A clinically useful, highly discriminating prognostic model remains elusive in stage I seminoma surveillance as we were unable to validate the previously developed model. However, primary tumor size retained prognostic importance and a scale of relapse risk based on the unit increment of tumor size was developed to help guide patients and clinicians in decision making.

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“…Still, increased knowledge of the small RNAs in tumor and blood samples has simplified the field of seminoma metastasis research. [54][55][56] Genomic changes that regulate a patient's germ cell tumor response to the vascular endothelial growth factor receptor (VEGFR) inhibitor sunitinib were evaluated by NGS, and the results revealed RET, EGFR, and KRAS amplification as relevant aberrations. 57 …”

Section: Ngs For Testicular Cancermentioning

confidence: 99%

Next-generation sequencing for endocrine cancers: Recent advances and challenges

et al. 2017

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Contemporary molecular biology research tools have enriched numerous areas of biomedical research that address challenging diseases, including endocrine cancers (pituitary, thyroid, parathyroid, adrenal, testicular, ovarian, and neuroendocrine cancers). These tools have placed several intriguing clues before the scientific community. Endocrine cancers pose a major challenge in health care and research despite considerable attempts by researchers to understand their etiology. Microarray analyses have provided gene signatures from many cells, tissues, and organs that can differentiate healthy states from diseased ones, and even show patterns that correlate with stages of a disease. Microarray data can also elucidate the responses of endocrine tumors to therapeutic treatments. The rapid progress in next-generation sequencing methods has overcome many of the initial challenges of these technologies, and their advantages over microarray techniques have enabled them to emerge as valuable aids for clinical research applications (prognosis, identification of drug targets, etc.). A comprehensive review describing the recent advances in next-generation sequencing methods and their application in the evaluation of endocrine and endocrine-related cancers is lacking. The main purpose of this review is to illustrate the concepts that collectively constitute our current view of the possibilities offered by next-generation sequencing technological platforms, challenges to relevant applications, and perspectives on the future of clinical genetic testing of patients with endocrine tumors. We focus on recent discoveries in the use of next-generation sequencing methods for clinical diagnosis of endocrine tumors in patients and conclude with a discussion on persisting challenges and future objectives.

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Discriminating metastasised from non-metastasised seminoma based on transcriptional changes in primary tumours using NGS

Cited by 9 publications

References 25 publications

The metastatic potential of seminomatous germ cell tumours is associated with a specific microRNA pattern

The metastatic potential of seminomatous germ cell tumours is associated with a specific microRNA pattern

Evaluation of a prognostic model for risk of relapse in stage I seminoma surveillance

Next-generation sequencing for endocrine cancers: Recent advances and challenges

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