The Road Ahead for Circulating microRNAs in Diagnosis and Management of Testicular Germ Cell Tumors

Lafin, John T.; Murray, Matthew J.; Frazier, A. Lindsay; Amatruda, James F.; Bagrodia, Aditya

doi:10.1007/s40291-021-00526-6

Cited by 6 publications

(9 citation statements)

References 17 publications

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“…Further investigations and validation of the protocol are warranted in different clinical contexts. In particular, it will be interesting to investigate if ddPCR may improve the follow-up of stage I patients on active surveillance, or aid in the assessment of marker-negative small testicular masses and viable germ cell malignancy in the post-chemotherapy metastatic context, to better personalize treatment and monitoring of TGCT patients (60).…”

Section: Discussionmentioning

confidence: 99%

DigiMir Test: Establishing a Novel Pipeline for MiR-371a Quantification Using Droplet Digital PCR in Liquid Biopsies From Testicular Germ Cell Tumor Patients

et al. 2022

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Testicular germ cell tumors (TGCTs) are the most common cancers in young-adult male patients aged between 15 and 39 years. Hsa-miR-371a-3p is currently the most reliable biomarker for diagnosis and monitoring of these patients non-invasively in liquid biopsies, and it is destined to be introduced in the clinic due to improved performance compared to the classical serum tumor markers available. Current studies have focused on real-time quantitative PCR (RT-qPCR) protocols for its determination; still, some challenges remain, since these protocols often require preamplification steps (costly and time-consuming), and report relative levels normalized to a housekeeping microRNA, not always performed the same way. Droplet digital PCR (ddPCR) shows the promise to overcome these challenges, skipping normalization and preamplifications, but has hardly been explored in the field of TGCTs. In this work, we provide a report of a ddPCR-based pipeline for the quantification of hsa-miR-371a-3p (the DigiMir pipeline) and compare it with two RT-qPCR protocols. A total of 107 plasma samples were investigated in the validation setting. The DigiMir pipeline detected TGCTs in a manner representative of tumor burden, with a sensitivity and specificity of 94% and 100%, respectively, outperforming the combined sensitivity of all three classical serum tumor markers (61.5%). Therefore, in this proof-of-concept investigation, we have shown that the DigiMir pipeline constitutes a new promising methodology to accurately report hsa-miR-371a-3p in the clinical setting.

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Section: Discussionmentioning

confidence: 99%

DigiMir Test: Establishing a Novel Pipeline for MiR-371a Quantification Using Droplet Digital PCR in Liquid Biopsies From Testicular Germ Cell Tumor Patients

et al. 2022

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“… 2 , 73 TE are characterized by chemoresistance and malignant potential, being commonly found in metastatic masses after chemotherapy as well as being independently associated with cancer specific mortality. 2 , 15 , 42 Elevated levels of miR-371a-3p have been found in the majority of patients with recurrent disease, detecting tumors less than 0.5 cm in diameter, 17 the sensitivity is lower than for detection of primary TGCT, owning to the larger percentage of TE in recurrent disease being found in 25–40% of resected lymph nodes, while 40–50% exhibit no signs of residual disease. 75 – 77 No combination of miRNAs adds to the diagnostic accuracy of miR-371a-3p and cannot reliably detect TE.…”

Section: Discussionmentioning

confidence: 99%

“… 72 , 77 , 79 , 80 Mir-885-5p and miR-448 were then suggested for TE detection, however, this could not be validated in further studies too. 17 , 72 , 77 , 79 The last small RNA sequencing study that was performed has not managed to verify any small RNA for TE detection. 77 With it clearly shown that there is no expression of STM in TE, 15 , 81 cfDNA analysis is currently the only proven method of TE detection.…”

Section: Discussionmentioning

confidence: 99%

“… 16 In light of this, accurate and non-invasive biomarkers are needed for more precise diagnosis, follow-up for disease progression and relapse detection, as well as to spare patients from a possibly unneeded radical orchiectomy. 2 , 13 , 17 Biomarker research centered on liquid biopsies (LBs) has promised to solve the problems of tissue biopsies and high tumor heterogeneity. 18 , 19 …”

Section: Introductionmentioning

confidence: 99%

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The utility of cfDNA in TGCT patient management: a systematic review

et al. 2022

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Background: Testicular germ cell tumors (TGCTs) are the most common young male malignancy with a steadily rising incidence. Standard clinical practice is radical orchidectomy of suspicious lumps followed by histopathological diagnosis and tumor subtyping. This practice can lead to complications and quality of life issues for the patients. Liquid biopsies, especially cell-free DNA (cfDNA), promised to be true surrogates for tissue biopsies, which are considered dangerous to perform in cases of testicular tumors. In this study, we have performed a systematic review on the potential of cfDNA in TGCT patient management, its potential challenges in translation to clinical application and possible approaches in further research. Materials & Methods: The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines on EuropePMC and PUBMED electronic databases, with the last update being on October 21, 2021. Due to the high heterogeneity in identified research articles, we have performed an overview of their efficacy. Results: Eight original articles have been identified on cfDNA in TGCT patients published from 2004 to 2021, of which six had more than one TGCT patient enrolled and were included in the final analysis. Three studies investigated cfDNA methylation, one has investigated mutations in cfDNA, two have investigated cfDNA amount, and one has investigated cfDNA integrity in TGCT. The sensitivity of cfDNA for TGCT was found to be higher than in serum tumor markers and lower than miR-371a-3p, with comparable specificity. cfDNA methylation analysis has managed to accurately detect teratoma in TGCT patients. Conclusion: Potential challenges in cfDNA application to TGCT patient management were identified. The challenges relating to the biology of TGCT with its low mutational burden and low cfDNA amounts in blood plasma make next-generation sequencing (NGS) methods especially challenging. We have also proposed possible approaches to help find clinical application, including a focus on cfDNA methylation analysis, and potentially solving the challenge of teratoma detection.

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“…Data have shown that it is possible to detect cancer through the detection of cancer-specific miRNAs in testicular germ cell cancer [ 32 ], colon cancer [ 33 ], ovarian cancer [ 34 , 35 ], gastric cancers [ 36 ], and breast cancer [ 37 ]. Multiple studies are currently ongoing to assess the potential of miRNA as an MRD biomarker in several cancers, such as breast cancer (NCT04720508), pancreatic cancer (NCT04406831), prostate cancer (NCT04835454), head and neck cancer (NCT04305366), and many others (source: , accessed on 26 April 2021).…”

Section: Introductionmentioning

confidence: 99%

Liquid Biopsy to Detect Minimal Residual Disease: Methodology and Impact

Honoré

Galot

Marcke

et al. 2021

Cancers

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One reason why some patients experience recurrent disease after a curative-intent treatment might be the persistence of residual tumor cells, called minimal residual disease (MRD). MRD cannot be identified by standard radiological exams or clinical evaluation. Tumor-specific alterations found in the blood indirectly diagnose the presence of MRD. Liquid biopsies thus have the potential to detect MRD, allowing, among other things, the detection of circulating tumor DNA (ctDNA), circulating tumor cells (CTC), or tumor-specific microRNA. Although liquid biopsy is increasingly studied, several technical issues still limit its clinical applicability: low sensitivity, poor standardization or reproducibility, and lack of randomized trials demonstrating its clinical benefit. Being able to detect MRD could give clinicians a more comprehensive view of the risk of relapse of their patients and could select patients requiring treatment escalation with the goal of improving cancer survival. In this review, we are discussing the different methodologies used and investigated to detect MRD in solid cancers, their respective potentials and issues, and the clinical impacts that MRD detection will have on the management of cancer patients.

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The Road Ahead for Circulating microRNAs in Diagnosis and Management of Testicular Germ Cell Tumors

Cited by 6 publications

References 17 publications

DigiMir Test: Establishing a Novel Pipeline for MiR-371a Quantification Using Droplet Digital PCR in Liquid Biopsies From Testicular Germ Cell Tumor Patients

DigiMir Test: Establishing a Novel Pipeline for MiR-371a Quantification Using Droplet Digital PCR in Liquid Biopsies From Testicular Germ Cell Tumor Patients

The utility of cfDNA in TGCT patient management: a systematic review

Liquid Biopsy to Detect Minimal Residual Disease: Methodology and Impact

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