BACKGROUND Breast cancer (BrC) remains the leading cause of cancer-related death in women, mainly due to recurrent and/or metastatic events, entailing the need for biomarkers predictive of progression to advanced disease. MicroRNAs hold promise as noninvasive cancer biomarkers due to their inherent stability and resilience in tissues and bodily fluids. There is increasing evidence that specific microRNAs play a functional role at different steps of the metastatic cascade, behaving as signaling mediators to enable the colonization of a specific organ. Herein, we aimed to evaluate the biomarker performance of microRNAs previously reported as associated with prognosis for predicting BrC progression in liquid biopsies. METHODS Selected microRNAs were assessed using a quantitative reverse transcription-polymerase chain reaction in a testing cohort of formalin-fixed paraffin-embedded primary (n = 16) and metastatic BrC tissues (n = 22). Then, miR-30b-5p and miR-200b-3p were assessed in a validation cohort #1 of formalin-fixed paraffin-embedded primary (n = 82) and metastatic BrC tissues (n = 93), whereas only miR-30b-5p was validated on a validation cohort #2 of liquid biopsies from BrC patients with localized (n = 20) and advanced (n = 25) disease. ROC curve was constructed to evaluate prognostic performance. RESULTS MiR-30b-5p was differentially expressed in primary tumors and paired metastatic lesions, with bone metastases displaying significantly higher miR-30b-5p expression levels, paralleling the corresponding primary tumors. Interestingly, patients with advanced disease disclosed increased circulating miR-30b-5p expression compared to patients with localized BrC. CONCLUSIONS MiR-30b-5p might identify BrC patients at higher risk of disease progression, thus, providing a useful clinical tool for patients' monitoring, entailing earlier and more effective treatment. Nonetheless, validation in larger multicentric cohorts is mandatory to confirm these findings.

中文翻译：

---

循环MiR-30b-5p的过表达可鉴定晚期乳腺癌。

背景技术乳腺癌（BrC）仍然是女性中与癌症相关的死亡的主要原因，这主要是由于复发和/或转移性事件所致，这需要对可预测进展为晚期疾病的生物标志物的需求。由于其固有的稳定性和在组织和体液中的弹性，MicroRNA具有作为无创性癌症生物标记物的潜力。越来越多的证据表明，特定的microRNA在转移级联反应的不同步骤中起着功能性作用，表现为能够使特定器官定居的信号传导介质。在本文中，我们旨在评估先前报道的与预测液体活检中BrC进展的预后相关的microRNA的生物标志物性能。方法在福尔马林固定石蜡包埋的原发性（n = 16）和转移性BrC组织（n = 22）的测试队列中，使用定量逆转录聚合酶链反应评估了选定的microRNA。然后，在福尔马林固定石蜡包埋的原发灶（n = 82）和转移性BrC组织（n = 93）的验证队列＃1中评估了miR-30b-5p和miR-200b-3p，而仅miR-30b-在来自本地（n = 20）和晚期（n = 25）疾病的BrC患者的液体活检验证队列＃2中验证了5p。构建ROC曲线以评估预后性能。结果MiR-30b-5p在原发性肿瘤和成对的转移性病变中差异表达，而骨转移显示出明显更高的miR-30b-5p表达水平，与相应的原发性肿瘤平行。有趣的是，与局部BrC患者相比，晚期疾病患者显示循环miR-​​30b-5p表达增加。结论MiR-30b-5p可能识别出具有较高疾病进展风险的BrC患者，从而为监测患者，提供更早更有效的治疗方法提供了有用的临床工具。但是，必须在较大的多中心队列中进行验证才能确认这些发现。