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Editorial by Bendu K. Konneh, John T. Lafin and Aditya Bagrodia on pp. 341-342 of this issue: MicroRNA-371a-3p as a blood-based biomarker in testis cancer |
Hamed Ahmadia,Thomas L. Jangb,Siamak Daneshmanda,Saum Ghodoussipourb,*( )
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a Department of Urology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA b Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA |
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Abstract MicroRNAs (miRNAs) are small noncoding RNAs involved in the regulation of mRNA transcription and translation, and possess all desirable features of an ideal tumor marker. Of almost 31 different miRNA clusters identified in germ cell tumors (GCTs), miR-371a-3p has shown exceptionally high sensitivity and specificity for both seminomatous and nonseminomatous GCTs. It is easily obtainable and correlates well with tumor burden. Recent multi-institutional prospective studies have shown promising test characteristics for miR-371a-3p as a diagnostic blood-based biomarker for GCT prior to orchiectomy including 80%-100% sensitivity and 90%-100% specificity. This accuracy may address other unmet needs in the management of patients with GCT. Early studies have suggested the utility of miR-371a-3p in detecting occult nodal metastasis in high-risk clinical stage I and early stage II disease. Ongoing clinical trials including SWOG 1823 and AGCT1531 are specifically designed to confirm the utility of miR-371a-3p in clinical stage I GCT. Despite its strong association with viable GCT after treatment with chemotherapy, miR-371a-3p does not seem to accurately predict the presence of teratoma in residual lesions. Also, standardization of extraction and interpretation methods is a necessary step to assure uniform results across different institutions.
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Received: 04 March 2021
Available online: 20 October 2021
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Corresponding Authors:
Saum Ghodoussipour
E-mail: saum.ghodoussipour@rutgers.edu
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Trial detail | SWOG S1823 (NCT04435756) | AGCT 1531 (NCT03067181) | Start date | - June 1, 2020 | - May 8, 2017 | Completion date | - April 1, 2025 (expected) | - June 30, 2027 (expected) | Enrollment, n | - 956 (estimated) | - 2059 (estimated) | Design | - Prospective observational cohort | - Multicenter randomized open label clinical trial | Arms | - Not applicable | - Arm I (bleomycin, carboplatin, and etoposide ×4). - Arm II (bleomycin, etoposide, and cisplatin ×4). - Arm III (bleomycin, carboplatin, and etoposide ×3). - Arm IV (bleomycin, etoposide, and cisplatin ×3). - Arm V (active surveillance for stage I GCT). | Stratification variables | - None defined | - None defined | Primary outcome | - Positive predictive value of microRNA-371 | - 2-year overall survival. - 2-year event free survival. | Secondary outcome | - Biobank of serial liquid biospecimens | - Percentage of hearing loss; - Percentage of peripheral neuropathy. | Inclusion criteria | - New diagnosis of a GCT confirmed pathologically or serologically. - All primary sites, stages, and histological subtypes of GCT are eligible; metachronous second primary GCTs are eligible. - If surgery is planned, male patients with clinical stage I testicular cancer must have orchiectomy completed within 42 days prior to registration. - Registered within 42 days after diagnosis and prior to initiation of a management plan or treatment for the disease. | - There is no age limit for the low risk stratum. - Newly diagnosed stage I GCT for low risk stratum; - Risk 1 group <11 years of age at enrollment. - Risk 2 group >11 and < 25 years of age at enrollment. - Stage II or higher for standard risk groups. - Histologic confirmation required. - All primary sites, and stages, histological subtypes of GCT are eligible. | Exclusion criteria | - None defined | - Pure teratoma; - Prior RPLND or chemotherapy. | Locations | - US and Canada | - US, Canada, Japan, New Zealand, Puerto Rico, and Saudi Arabia |
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Current trials on the role of microRNA-371 in early stage GCT.
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