Discipline of Surgery, School of Medicine, Lambe Institute for Translational Research, National University of Ireland, Galway, Ireland.
Mol Cancer. 2022 Apr 4;21(1):95. doi: 10.1186/s12943-022-01506-y.
Breast cancer continues to be a major global problem with significant mortality associated with advanced stage and metastases at clinical presentation. However, several findings suggest that metastasis is indeed an early occurrence. The standard diagnostic techniques such as invasive core needle biopsy, serological protein marker assays, and non-invasive radiological imaging do not provide information about the presence and molecular profile of small fractions of early metastatic tumor cells which are prematurely dispersed in the circulatory system. These circulating tumor cells (CTCs) diverge from the primary tumors as clusters with a defined secretome comprised of circulating cell-free nucleic acids and small microRNAs (miRNAs). These circulatory biomarkers provide a blueprint of the mutational profile of the tumor burden and tumor associated alterations in the molecular signaling pathways involved in oncogenesis. Amidst the multitude of circulatory biomarkers, miRNAs serve as relatively stable and precise biomarkers in the blood for the early detection of CTCs, and promote step-wise disease progression by executing paracrine signaling that transforms the microenvironment to guide the metastatic CTCs to anchor at a conducive new organ. Random sampling of easily accessible patient blood or its serum/plasma derivatives and other bodily fluids collectively known as liquid biopsy (LB), forms an efficient alternative to tissue biopsies. In this review, we discuss in detail the divergence of early metastases as CTCs and the involvement of miRNAs as detectable blood-based diagnostic biomarkers that warrant a timely screening of cancer, serial monitoring of therapeutic response, and the dynamic molecular adaptations induced by miRNAs on CTCs in guiding primary and second-line systemic therapy.
乳腺癌仍然是一个全球性的重大问题，其死亡率与临床发病时的晚期和转移密切相关。然而，有几项研究结果表明，转移实际上是一个早期事件。标准的诊断技术，如侵入性核心针活检、血清蛋白标志物检测和非侵入性影像学检查，都无法提供有关早期转移性肿瘤细胞的存在和分子特征的信息，这些细胞在循环系统中过早地分散。这些循环肿瘤细胞（CTC）与原发性肿瘤不同，它们以簇的形式存在，具有特定的分泌组，包括循环细胞游离核酸和小 microRNAs（miRNAs）。这些循环生物标志物提供了肿瘤负担的突变特征和肿瘤相关的分子信号通路改变的蓝图，这些改变与肿瘤发生有关。在众多的循环生物标志物中，miRNAs 作为血液中相对稳定和精确的 CTC 早期检测标志物，通过执行旁分泌信号来促进疾病的逐步进展，这种信号改变微环境以指导转移性 CTC 锚定在有利的新器官。对容易获得的患者血液或其血清/血浆衍生物以及其他体液（统称为液体活检（LB））的随机采样，是组织活检的有效替代方法。在这篇综述中，我们详细讨论了早期转移作为 CTC 的分化以及 miRNAs 作为可检测的基于血液的诊断生物标志物的作用，这些标志物需要及时筛查癌症、对治疗反应进行连续监测以及 miRNA 对 CTC 诱导的动态分子适应，以指导一线和二线系统治疗。
