Context

Clinical management of testicular germ cell tumours (GCTs) is hampered by low sensitivity and specificity of the biomarkers currently in use. Circulating microRNAs (miRs) might offer the potential to address areas of unmet clinical need.

Objective

To systematically evaluate the evidence for clinical applications of serum levels of miR302/367 and miR371-3 in adult testicular GCTs in terms of primary diagnosis, various clinical scenarios, and the costs of clinical implementation.

Evidence acquisition

We performed a critical review of PubMed/Medline, Embase and the Cochrane Library in January 2021 in accordance with Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement.

Evidence synthesis

Thirty-one manuscripts addressed miR performance and potential clinical use in testicular GCT. Of these, 23 evaluated the utility in primary diagnosis, seven in early-stage disease, and 13 in metastatic disease, and two addressed the costs of clinical implementation. Of the various miRs studied, miR-371a-3p appears the most useful and potentially the only one that needs to be assayed, with an area under the receiver operating characteristic curve >0.90, sensitivity of 89–96%, and specificity of >90% for both seminoma and nonseminoma, surpassing the classic serum tumour markers. The miRs studied to date are not elevated in cases with teratoma only. Levels of miR-371a-3p correlate with primary tumour mass, clinical stage, and International Germ Cell Cancer Collaborative Group risk groups. Serial measurements mirror treatment efficacy in all clinical stages.

Conclusions

Circulating miRNA levels, particularly of miR-371a-3p, have potential for incorporation in clinical practice and may aid in clinical decision-making in various clinical scenarios in GCT.

Patient summary

We analysed the current evidence on the usefulness of blood levels of molecules called microRNAs in the management of testicular tumours. The microRNA-371a-3p molecule has better sensitivity and specificity than the markers currently being measured. This new biomarker may soon have a place in clinical practice.

中文翻译：

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循环微小RNA，睾丸生殖细胞肿瘤中的下一代血清生物标志物：系统评价

语境

睾丸生殖细胞肿瘤 (GCT) 的临床管理因目前使用的生物标志物的低敏感性和特异性而受到阻碍。循环 microRNAs (miRs) 可能提供解决未满足临床需求领域的潜力。

客观的

从初步诊断、各种临床情景和临床实施成本方面系统评估成人睾丸 GCT 中血清 miR302/367 和 miR371-3 水平的临床应用证据。

取证

我们根据系统评价和荟萃分析的首选报告项目 (PRISMA) 声明，于 2021 年 1 月对 PubMed/Medline、Embase 和 Cochrane 图书馆进行了严格审查。

证据综合

31 篇手稿讨论了 miR 在睾丸 GCT 中的性能和潜在的临床用途。其中，23 项评估了初级诊断的效用，7 项评估了早期疾病的效用，13 项评估了转移性疾病的效用，2 项评估了临床实施的成本。在所研究的各种 miRs 中，miR-371a-3p 似乎是最有用的，并且可能是唯一需要检测的，其受试者工作特征曲线下面积 > 0.90，灵敏度为 89-96%，特异性 > 90 % 为精原细胞瘤和非精原细胞瘤，超过了经典的血清肿瘤标志物。迄今为止研究的 miRs 仅在畸胎瘤病例中没有升高。miR-371a-3p 的水平与原发性肿瘤块、临床分期和国际生殖细胞癌协作组风险组相关。

结论

循环 miRNA 水平，特别是 miR-371a-3p，具有纳入临床实践的潜力，并可能有助于 GCT 各种临床情况下的临床决策。

患者总结

我们分析了目前关于血液中称为 microRNA 的分子水平在治疗睾丸肿瘤中的有用性的证据。microRNA-371a-3p分子比目前正在测量的标记物具有更好的敏感性和特异性。这种新的生物标志物可能很快就会在临床实践中占有一席之地。