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纵向监测显示转移性结直肠癌患者化疗后循环肿瘤细胞(CTCs)及其相关 microRNAs 发生动态变化。

Longitudinal monitoring reveals dynamic changes in circulating tumor cells (CTCs) and CTC-associated miRNAs in response to chemotherapy in metastatic colorectal cancer patients.

机构信息

Department of Laboratory Medicine, National University Hospital, Singapore.

Department of Pathology, National University, Singapore.

出版信息

Cancer Lett. 2018 Jun 1;423:1-8. doi: 10.1016/j.canlet.2018.02.039. Epub 2018 Mar 5.

Abstract

We evaluated the changes in CTC count and CTC-associated miRNAs during the course of chemotherapy in patients with metastatic colorectal cancer. Blood samples were collected from 9 metastatic colorectal cancer patients prior to chemotherapy and at every other chemotherapy session during the course of treatment. CTCs were isolated and enumerated using a size-exclusion method (CellSievo, Singapore). CTC-associated miRNAs were isolated using a paper-based, partitioning method, and analyzed using reverse transcription quantitative real-time PCR (MiRXES, Singapore). CTC count trends generally correlated with disease progression defined by radiological measurements and trends in carcinoembryonic antigen (CEA) levels; hence CTC counts may be useful in cases where CEA is not elevated. CTC-associated miRNAs identified were miR-15b, miR-16, miR-19a, miR-21, miR-25, miR-30d, miR-126, miR-185, miR-221, miR-222, and miR-324-5p. The expression of CTC-associated miRNAs did not appear to correlate with CTC count and exhibited inter-individual heterogeneity. This pilot study suggests that analysis of CTC changes during the course of treatment may be useful in monitoring response to therapy in metastatic colorectal cancer.

摘要

我们评估了转移性结直肠癌患者化疗过程中循环肿瘤细胞(CTC)计数和 CTC 相关微小 RNA(miRNA)的变化。在化疗前和治疗过程中的每一次化疗时,采集了 9 名转移性结直肠癌患者的血样。使用基于大小排除的方法(CellSievo,新加坡)分离和计数 CTC。使用基于纸张的分区方法分离 CTC 相关 miRNA,并使用逆转录定量实时 PCR(MiRXES,新加坡)进行分析。CTC 计数趋势通常与影像学测量定义的疾病进展和癌胚抗原(CEA)水平的趋势相关;因此,在 CEA 不升高的情况下,CTC 计数可能有用。鉴定的 CTC 相关 miRNA 为 miR-15b、miR-16、miR-19a、miR-21、miR-25、miR-30d、miR-126、miR-185、miR-221、miR-222 和 miR-324-5p。CTC 相关 miRNA 的表达似乎与 CTC 计数无关,并且表现出个体间的异质性。这项初步研究表明,在治疗过程中分析 CTC 变化可能有助于监测转移性结直肠癌的治疗反应。

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