研究动态
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循环肿瘤细胞相关的微小RNA谱在化疗放疗期间发生变化,并且对局部晚期直肠癌的反应具有预测能力。

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

发表日期:2023 Aug 20
作者: Stephanie H Lim, Wei Chua, Weng Ng, Emilia Ip, Tania M Marques, Nham T Tran, Margarida Gama-Carvalho, Ray Asghari, Christopher Henderson, Yafeng Ma, Paul de Souza, Kevin J Spring
来源: Cancers

摘要:

局部进展的直肠癌(LARC)传统上被以三种疗法治疗,包括新辅助放疗+/-化疗,手术和辅助化疗。目前临床上需要生物标志物来预测治疗反应和预后,尤其是在新辅助治疗期间。液体活检以循环肿瘤细胞(CTCs)和其中的循环核酸,特别是微小RNA(miRNA)是一种新颖的方法,后者还是疾病高度稳定且临床相关的调控因子。我们研究了一个52例LARC患者的前瞻性队列,并在基线,治疗期间和治疗后获得样本。我们在化疗放疗期间,在这三个时间点使用IsofluxTM(Fluxion Biosciences Inc., Alameda, CA, USA)CTC分离和检测平台进行CTC计数。然后,我们对分离的CTCs进行miRNA表达分析,使用了106个miRNA候选基因。我们发现,在73%的患者基线时有CTCs存在;CTC数量在治疗过程中下降,而miRNA表达谱也发生了变化。在基线和治疗期间(第3周)时间点之间,有三个微小RNA(hsa-miR-95,hsa-miR-10a和hsa-miR-16-1*)表达差异非常大。重要的是,我们发现hsa-miR-19b-3p和hsa-miR-483-5p与良好的治疗反应相关。后者(hsa-miR-483-5p)在良好反应者和差劲反应者之间也表达差异。这些miRNA代表了潜在的预测性生物标志物,因此也是潜在的基于miRNA的治疗策略。在这项研究中,我们证明CTCs存在于非转移早期癌症环境中且可被分离,并且其相关的miRNA谱可以潜在地用于预测治疗反应。
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.