Lucia Nappi1, Marisa Thi2, Nabil Adra3, Robert J Hamilton4, Ricardo Leao5, Jean-Michel Lavoie6, Maryam Soleimani7, Bernhard J Eigl7, Kim Chi7, Martin Gleave2, Alan So2, Peter C Black2, Robert Bell2, Siamak Daneshmand8, Clint Cary3, Timothy Masterson3, Lawrence Einhorn3, Craig Nichols9, Christian Kollmannsberger10. 1. Department of Medicine, Medical Oncology Division, BC Cancer, Vancouver Centre, University of British Columbia, Vancouver, BC, Canada; Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada. 2. Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada. 3. Indiana University Simon Comprehensive Cancer Center, Indianapolis, IN, USA. 4. Department of Surgery (Urology), Princess Margaret Cancer Centre, Toronto, ON, Canada. 5. Hospital CUF Coimbra, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. 6. Department of Medical Oncology, British Columbia Cancer, Surrey Centre, Surrey, BC, Canada. 7. Department of Medicine, Medical Oncology Division, BC Cancer, Vancouver Centre, University of British Columbia, Vancouver, BC, Canada. 8. Department of Urology, University of South California, Los Angeles, CA, USA. 9. Testicular Cancer Commons, Beaverton, OR, USA; SWOG Group Chairs Office, Portland, OR, USA. 10. Department of Medicine, Medical Oncology Division, BC Cancer, Vancouver Centre, University of British Columbia, Vancouver, BC, Canada. Electronic address: ckollmannsberger@bccancer.bc.ca.
Abstract
Active germ cell malignancies express high levels of specific circulating micro-RNAs (miRNAs), including miR-371a-3p (miR371), which is undetectable in teratoma. Teratoma markers are urgently needed for theselection of patients and treatments because of the risk of malignant transformation and growing teratoma syndrome. To assess the accuracy of plasma miR375 alone or in combination with miR371 in detecting teratoma, 100 germ cell tumor patients, divided into two cohorts, were enrolled in a prospective multi-institutional study. In the discovery cohort, patients with pure teratoma and with no/low risk of harboring teratoma were compared; the validation cohort included patients with confirmed teratoma, active germ cell malignancy, or complete response after chemotherapy. The area under the receiver operating characteristic curve values for miR375, miR371, and miR371-miR375 were, respectively, 0.93 (95% confidence interval [CI]: 0.87-0.99), 0.59 (95% CI: 0.44-0.73), and 0.95 (95% CI: 0.90-0.99) in the discovery cohort and 0.55 (95% CI: 0.36-0.74), 0.74 (95% CI: 0.58-0.91), and 0.77 (95% CI: 0.62-0.93) in the validation cohort. Our study demonstrated that the plasma miR371-miR375 integrated evaluation is highly accurate to detect teratoma. PATIENT SUMMARY: The evaluation of two micro-RNAs (miR375-miR371) in the blood of patients with germ cell tumors is promising to predict teratoma. This test could be particularly relevant to the identification of teratoma in patients with postchemotherapy residual disease.
Active germ cell malignancies express high levels of specific circulating micro-RNAs (miRNAs), including miR-371a-3p (miR371), which is undetectable in teratoma. Teratoma markers are urgently needed for theselection of patients and treatments because of the risk of malignant transformation and growing teratoma syndrome. To assess the accuracy of plasma miR375 alone or in combination with miR371 in detecting teratoma, 100 germ cell tumorpatients, divided into two cohorts, were enrolled in a prospective multi-institutional study. In the discovery cohort, patients with pure teratoma and with no/low risk of harboring teratoma were compared; the validation cohort included patients with confirmed teratoma, active germ cell malignancy, or complete response after chemotherapy. The area under the receiver operating characteristic curve values for miR375, miR371, and miR371-miR375 were, respectively, 0.93 (95% confidence interval [CI]: 0.87-0.99), 0.59 (95% CI: 0.44-0.73), and 0.95 (95% CI: 0.90-0.99) in the discovery cohort and 0.55 (95% CI: 0.36-0.74), 0.74 (95% CI: 0.58-0.91), and 0.77 (95% CI: 0.62-0.93) in the validation cohort. Our study demonstrated that the plasma miR371-miR375 integrated evaluation is highly accurate to detect teratoma. PATIENT SUMMARY: The evaluation of two micro-RNAs (miR375-miR371) in the blood of patients with germ cell tumors is promising to predict teratoma. This test could be particularly relevant to the identification of teratoma in patients with postchemotherapy residual disease.
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