文章：

循环肿瘤细胞相关微小RNA谱在放化疗期间发生变化，并对局部晚期直肠癌的治疗反应具有预测价值

Circulating Tumour Cell Associated MicroRNA Profiles Change during Chemoradiation and Are Predictive of Response in Locally Advanced Rectal Cancer

原文发布日期：20 August 2023

DOI: 10.3390/cancers15164184

类型: Article

开放获取: 是

英文摘要：

Locally advanced rectal cancer (LARC) has traditionally been treated with trimodality therapy consisting of neoadjuvant radiation +/− chemotherapy, surgery, and adjuvant chemotherapy. There is currently a clinical need for biomarkers to predict treatment response and outcomes, especially during neoadjuvant therapy. Liquid biopsies in the form of circulating tumour cells (CTCs) and circulating nucleic acids in particular microRNAs (miRNA) are novel, the latter also being highly stable and clinically relevant regulators of disease. We studied a prospective cohort of 52 patients with LARC, and obtained samples at baseline, during treatment, and post-treatment. We enumerated CTCs during chemoradiation at these three time-points, using the IsofluxTM(Fluxion Biosciences Inc., Alameda, CA, USA) CTC Isolation and detection platform. We then subjected the isolated CTCs to miRNA expression analyses, using a panel of 106 miRNA candidates. We identified CTCs in 73% of patients at baseline; numbers fell and miRNA expression profiles also changed during treatment. Between baseline and during treatment (week 3) time-points, three microRNAs (hsa-miR-95, hsa-miR-10a, and hsa-miR-16-1*) were highly differentially expressed. Importantly, hsa-miR-19b-3p and hsa-miR-483-5p were found to correlate with good response to treatment. The latter (hsa-miR-483-5p) was also found to be differentially expressed between good responders and poor responders. These miRNAs represent potential predictive biomarkers, and thus a potential miRNA-based treatment strategy. In this study, we demonstrate that CTCs are present and can be isolated in the non-metastatic early-stage cancer setting, and their associated miRNA profiles can potentially be utilized to predict treatment response.

摘要翻译： 

局部进展期直肠癌传统上采用新辅助放疗联合或不联合化疗、手术及辅助化疗的三联疗法。目前临床上亟需能够预测治疗反应及预后的生物标志物，特别是在新辅助治疗阶段。以循环肿瘤细胞和循环核酸（尤其是微小RNA）形式存在的液体活检是新兴技术，后者作为疾病调控因子具有高度稳定性及临床相关性。本研究纳入52例局部进展期直肠癌患者的前瞻性队列，在基线期、治疗期间及治疗后采集样本。采用IsofluxTM循环肿瘤细胞分离检测平台，在放化疗期间的三个时间点对循环肿瘤细胞进行计数。随后对分离的循环肿瘤细胞进行微小RNA表达谱分析，检测106种候选微小RNA。基线期73%的患者检出循环肿瘤细胞；治疗期间细胞数量下降，微小RNA表达谱亦发生改变。在基线期与治疗期间（第3周）两个时间点，三种微小RNA（hsa-miR-95、hsa-miR-10a和hsa-miR-16-1*）呈现显著差异表达。值得注意的是，hsa-miR-19b-3p和hsa-miR-483-5p与良好治疗反应相关，其中hsa-miR-483-5p在治疗反应良好者与不良者间存在差异表达。这些微小RNA可作为潜在的预测性生物标志物，为基于微小RNA的治疗策略提供新思路。本研究证实，在非转移性早期癌症中可检测并分离循环肿瘤细胞，其相关微小RNA谱有望用于预测治疗反应。

原文链接：

Circulating Tumour Cell Associated MicroRNA Profiles Change during Chemoradiation and Are Predictive of Response in Locally Advanced Rectal Cancer