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Utility of Serum miR-371a-3p in Predicting Relapse on Surveillance in Patients with Clinical Stage I Testicular Germ
João Lobo1, Ricardo Leão2, Ad J M Gillis3
1Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands; Cancer Biology and Epigenetics Group, Portuguese Oncology Institute of Porto (IPOP), Research Center and Porto Comprehensive Cancer Center (P.CCC), Porto, Portugal; Department of Pathology, Portuguese Oncology Institute of Porto (IPOP), Porto, Portugal; Department of Pathology and Molecular Immunology, Biomedical Sciences Institute Abel Salazar, University of Porto (ICBAS-UP), Porto, Portugal.
Background:
Optimal management of clinical stage I (CSI) testicular cancer is controversial due to lack of robust prognostic factors; miRNA-371a-3p holds promise as a biomarker, although its clinical utility for identifying patients at risk of relapse is unknown.
Objective:
To explore the association between serum miR-371a-3p and CSI surveillance relapse.
Design, Setting, And Participants:
Serial banked sera from 151 CSI (101 seminomas and 50 nonseminomatous germ cell tumors [NSGCTs]) samples from our Princess Margaret active surveillance cohort were tested.
Outcome Measurements And Statistical Analysis:
Using the ampTSmiR test, miR-371a-3p was assayed. Multivariate logistic regression was used to assess the association between postorchiectomy miRNA and relapse.
Results And Limitations:
Thirty-four (23%) patients relapsed. There was no association between postorchiectomy miR-371a-3p (2.43 vs 2.74, p = 0.31) or percent decline from before to after orchiectomy (95.8% vs 93.1%, p = 0.14) and relapse. After adjustment for clinical prognostic factors, there remained no association between postorchiectomy miR-371a-3p and relapse (seminoma: odds ratio [OR] 1.33, 95% confidence interval [CI] 0.87-2.02, p = 0.18; NSGCT: OR 0.45, 95% CI 0.21-1.00, p = 0.05). Postorchiectomy miR-371a-3p levels rose as the date of miRNA assessment approached relapse. At relapse, serum markers alpha-fetoprotein and human chorionic gonadotropin were normal in 62%; yet, miR-371a-3p was elevated in 32/34 (94.1%). The magnitude of miR-371a-3p elevation at relapse correlated with disease burden (N1/M0 122.5 vs N2-N3/M0: 521.1; p = 0.05). Limitations include small numbers of relapses and variable time points of serum collection.
Conclusions:
In our cohort of CSI testis cancer patients on surveillance, postorchiectomy miR-371a-3p levels were not associated with relapse, suggesting that miR-371a-3p may not be a useful biomarker for guiding adjuvant therapy. Our data suggest that miR-371a-3p holds potential as an early relapse marker and warrants a prospective study, as this may allow a window for less morbid relapse therapy.
Patient Summary:
The promising novel blood biomarker for testis cancer miR-371a-3p may not provide information at testicle removal, but serial monitoring may lead to earlier detection of relapse.
