Princess 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.
Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Hospital CUF Coimbra, Department of Urology, Hospital de Braga, Braga, Portugal; Departments of Surgery (Urology), Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada.
Eur Urol Oncol. 2021 Jun;4(3):483-491. doi: 10.1016/j.euo.2020.11.004. Epub 2020 Dec 4.
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.
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.
Using the ampTSmiR test, miR-371a-3p was assayed. Multivariate logistic regression was used to assess the association between postorchiectomy miRNA and relapse.
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.
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.
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.
由于缺乏强有力的预后因素，Ⅰ期（CSI）睾丸癌的最佳治疗方案仍存在争议；miRNA-371a-3p 有望成为一种生物标志物，尽管其用于识别复发风险患者的临床应用尚不清楚。
探讨血清 miR-371a-3p 与 CSI 监测复发的关系。
设计、地点和参与者：对来自我们玛格丽特公主主动监测队列的 151 例 CSI（101 例精原细胞瘤和 50 例非精原细胞瘤生殖细胞肿瘤[NSGCT]）样本的连续储存血清进行了检测。
使用 ampTSmiR 检测法检测 miR-371a-3p。采用多变量逻辑回归分析睾丸切除术后 miRNA 与复发之间的关系。
34 例（23%）患者复发。睾丸切除术后 miR-371a-3p（2.43 比 2.74，p=0.31）或睾丸切除术后下降百分比（95.8%比 93.1%，p=0.14）与复发均无相关性。调整临床预后因素后，睾丸切除术后 miR-371a-3p 与复发之间仍无相关性（精原细胞瘤：优势比[OR]1.33，95%置信区间[CI]0.87-2.02，p=0.18；NSGCT：OR 0.45，95%CI 0.21-1.00，p=0.05）。睾丸切除术后 miR-371a-3p 水平随着 miRNA 评估日期接近复发而升高。在复发时，血清标志物甲胎蛋白和人绒毛膜促性腺激素在 62%的患者中正常；然而，34/34 例（94.1%）患者的 miR-371a-3p 升高。复发时 miR-371a-3p 升高的幅度与疾病负担相关（N1/M0 为 122.5 比 N2-N3/M0：521.1；p=0.05）。局限性包括复发例数少和血清采集时间点不同。
在我们的 CSI 睾丸癌患者监测队列中，睾丸切除术后 miR-371a-3p 水平与复发无关，提示 miR-371a-3p 可能不是指导辅助治疗的有用生物标志物。我们的数据表明，miR-371a-3p 具有作为早期复发标志物的潜力，值得进行前瞻性研究，因为这可能为较少病态复发治疗提供一个窗口。
有前途的新型睾丸癌血液生物标志物 miR-371a-3p 在睾丸切除术后可能无法提供信息，但连续监测可能会更早地发现复发。
