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基于液体活检的方法监测结直肠癌术后患者的治疗反应。

A Liquid Biopsy-Based Approach for Monitoring Treatment Response in Post-Operative Colorectal Cancer Patients.

机构信息

Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary.

Molecular Medicine Research Group, Eötvös Loránd Research Network, 1083 Budapest, Hungary.

出版信息

Int J Mol Sci. 2022 Mar 29;23(7):3774. doi: 10.3390/ijms23073774.

DOI:10.3390/ijms23073774
PMID:35409133
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8998310/
Abstract

Monitoring the therapeutic response of colorectal cancer (CRC) patients is crucial to determine treatment strategies; therefore, we constructed a liquid biopsy-based approach for tracking tumor dynamics in non-metastatic (nmCRC) and metastatic (mCRC) patients (n = 55). Serial blood collections were performed during chemotherapy for measuring the amount and the global methylation pattern of cell-free DNA (cfDNA), the promoter methylation of SFRP2 and SDC2 genes, and the plasma homocysteine level. The average cfDNA amount was higher (p < 0.05) in nmCRC patients with recurrent cancer (30.4 ± 17.6 ng) and mCRC patients with progressive disease (PD) (44.3 ± 34.5 ng) compared to individuals with remission (13.2 ± 10.0 ng) or stable disease (12.5 ± 3.4 ng). More than 10% elevation of cfDNA from first to last sample collection was detected in all recurrent cases and 92% of PD patients, while a decrease was observed in most patients with remission. Global methylation level changes indicated a decline (75.5 ± 3.4% vs. 68.2 ± 8.4%), while the promoter methylation of SFRP2 and SDC2 and homocysteine level (10.9 ± 3.4 µmol/L vs. 13.7 ± 4.3 µmol/L) presented an increase in PD patients. In contrast, we found exact opposite changes in remission cases. Our study offers a more precise blood-based approach to monitor the treatment response to different chemotherapies than the currently used markers.

摘要

监测结直肠癌（CRC）患者的治疗反应对于确定治疗策略至关重要；因此，我们构建了一种基于液体活检的方法，用于跟踪非转移性（nmCRC）和转移性（mCRC）患者的肿瘤动态（n = 55）。在化疗期间进行了多次血液采集，以测量游离 DNA（cfDNA）的数量和整体甲基化模式、SFRP2 和 SDC2 基因的启动子甲基化以及血浆同型半胱氨酸水平。与缓解（13.2 ± 10.0 ng）或稳定疾病（12.5 ± 3.4 ng）患者相比，复发癌症（30.4 ± 17.6 ng）和进展性疾病（PD）（44.3 ± 34.5 ng）的 nmCRC 患者和 mCRC 患者的平均 cfDNA 量更高（p < 0.05）。在所有复发病例中均检测到从第一次到最后一次样本采集时 cfDNA 升高超过 10%，92%的 PD 患者升高超过 10%，而大多数缓解患者的 cfDNA 则下降。全球甲基化水平的变化表明下降（75.5 ± 3.4% 对 68.2 ± 8.4%），而 SFRP2 和 SDC2 的启动子甲基化和同型半胱氨酸水平（10.9 ± 3.4 µmol/L 对 13.7 ± 4.3 µmol/L）在 PD 患者中升高。相比之下，我们在缓解病例中发现了完全相反的变化。我们的研究提供了一种比目前使用的标志物更精确的基于血液的方法来监测不同化疗药物的治疗反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1427/8998310/5d6e77f0948b/ijms-23-03774-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1427/8998310/97e00318d7ec/ijms-23-03774-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1427/8998310/f948a6ce4616/ijms-23-03774-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1427/8998310/c72b21330b86/ijms-23-03774-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1427/8998310/4235f82b6d01/ijms-23-03774-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1427/8998310/5d6e77f0948b/ijms-23-03774-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1427/8998310/97e00318d7ec/ijms-23-03774-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1427/8998310/f948a6ce4616/ijms-23-03774-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1427/8998310/c72b21330b86/ijms-23-03774-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1427/8998310/4235f82b6d01/ijms-23-03774-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1427/8998310/5d6e77f0948b/ijms-23-03774-g005.jpg

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