Rohit R Badia1, Dreaux Abe1, Daniel Wong1, Nirmish Singla1, Anna Savelyeva1, Nathan Chertack1, Solomon L Woldu1, Yair Lotan1, Ryan Mauck1, Dan Ouyang1, Xiaosong Meng1, Cheryl M Lewis2, Kuntal Majmudar2, Liwei Jia2, Payal Kapur2, Lin Xu3, A Lindsay Frazier4, Vitaly Margulis1,5, Douglas W Strand1, Nicholas Coleman6, Matthew J Murray6,7, James F Amatruda8, John T Lafin1, Aditya Bagrodia1. 1. Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas. 2. Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas. 3. Quantitative Biomedical Research Center, Department of Population & Data Sciences, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas. 4. Dana-Farber/Boston Children's Cancer and Blood Disorder Center, Boston, Massachusetts. 5. Department of Urology, I.M. Sechenov First Moscow State University. 6. Department of Pathology, University of Cambridge, UK. 7. Department of Pediatric Hematology and Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. 8. Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Departments of Pediatrics and Medicine, Keck School of Medicine, University of Southern California.
Abstract
PURPOSE: Current serum tumor markers for testicular germ cell tumor are limited by low sensitivity. Growing evidence supports the use of circulating miR-371a-3p as a superior marker for malignant (viable) germ cell tumor management. We evaluated the real-world application of serum miR-371a-3p levels in detecting viable germ cell tumor among patients undergoing partial or radical orchiectomy. MATERIALS AND METHODS: Serum samples were collected from 69 consecutive patients before orchiectomy. Performance characteristics of serum miR-371a-3p were compared with conventional serum tumor markers (⍺-fetoprotein/β-human chorionic gonadotropin/lactate dehydrogenase) between patients with viable germ cell tumor and those without viable germ cell tumor on orchiectomy pathology. Relative miR-371a-3p levels were correlated with clinical course. The Kruskal-Wallis test and linear and ordinal regression models were used for analysis. RESULTS: For detecting viable germ cell tumor, combined conventional serum tumor markers had a specificity of 100%, sensitivity of 58% and AUC of 0.79. The miR-371a-3p test showed a specificity of 100%, sensitivity of 93% and AUC of 0.978. Median relative expression of miR-371a-3p in viable germ cell tumor cases was more than 6,800-fold higher than in those lacking viable germ cell tumor. miR-371a-3p levels correlated with composite stage (p=0.006) and, among composite stage I cases, independently associated with embryonal carcinoma percentage (p=0.0012) and tumor diameter (p <0.0001). Six patients underwent orchiectomy after chemotherapy and were correctly predicted to have presence or absence of viable germ cell tumor by the miR-371a-3p test. CONCLUSIONS: If validated, the miR-371a-3p test can be used in conjunction with conventional serum tumor markers to aid clinical decision making. A positive miR-371a-3p test in patients after preoperative chemotherapy or with solitary testes could potentially guide subsequent orchiectomy or observation.
PURPOSE: Current serum tumor markers for testicular germ cell tumor are limited by low sensitivity. Growing evidence supports the use of circulating miR-371a-3p as a superior marker for malignant (viable) germ cell tumor management. We evaluated the real-world application of serum miR-371a-3p levels in detecting viable germ cell tumor among patients undergoing partial or radical orchiectomy. MATERIALS AND METHODS: Serum samples were collected from 69 consecutive patients before orchiectomy. Performance characteristics of serum miR-371a-3p were compared with conventional serum tumor markers (⍺-fetoprotein/β-human chorionic gonadotropin/lactate dehydrogenase) between patients with viable germ cell tumor and those without viable germ cell tumor on orchiectomy pathology. Relative miR-371a-3p levels were correlated with clinical course. The Kruskal-Wallis test and linear and ordinal regression models were used for analysis. RESULTS: For detecting viable germ cell tumor, combined conventional serum tumor markers had a specificity of 100%, sensitivity of 58% and AUC of 0.79. The miR-371a-3p test showed a specificity of 100%, sensitivity of 93% and AUC of 0.978. Median relative expression of miR-371a-3p in viable germ cell tumor cases was more than 6,800-fold higher than in those lacking viable germ cell tumor. miR-371a-3p levels correlated with composite stage (p=0.006) and, among composite stage I cases, independently associated with embryonal carcinoma percentage (p=0.0012) and tumor diameter (p <0.0001). Six patients underwent orchiectomy after chemotherapy and were correctly predicted to have presence or absence of viable germ cell tumor by the miR-371a-3p test. CONCLUSIONS: If validated, the miR-371a-3p test can be used in conjunction with conventional serum tumor markers to aid clinical decision making. A positive miR-371a-3p test in patients after preoperative chemotherapy or with solitary testes could potentially guide subsequent orchiectomy or observation.
Entities:
Keywords:
biomarkers; germ cell and embryonal; microRNAs; neoplasms; testicular neoplasms
Authors: Adriana Fonseca; João Lobo; Florette K Hazard; Joanna Gell; Peter K Nicholls; Robert S Weiss; Lindsay Klosterkemper; Samuel L Volchenboum; James C Nicholson; A Lindsay Frazier; James F Amatruda; Aditya Bagrodia; Michelle Lockley; Matthew J Murray Journal: Br J Cancer Date: 2022-10-13 Impact factor: 9.075
Authors: Jesse Ory; Udi Blankstein; Daniel C Gonzalez; Aditya A Sathe; Joshua T White; Carlos Delgado; John Reynolds; Keith Jarvi; Ranjith Ramasamy Journal: BJUI Compass Date: 2021-02-23
Authors: José Pedro Sequeira; João Lobo; Vera Constâncio; Tiago Brito-Rocha; Carina Carvalho-Maia; Isaac Braga; Joaquina Maurício; Rui Henrique; Carmen Jerónimo Journal: Front Oncol Date: 2022-06-10 Impact factor: 5.738