PO.CL01.08 · 临床研究

一部分转移性结直肠癌患者中循环肿瘤DNA的夜间升高

Nocturnal rise in circulating tumor DNA in a subset of metastatic colorectal cancer patients

编号 2592 展板 11 时间 4/20 09:00–12:00 区域 Section 46 主讲 Ekaterina Kuligina, PhD

分会场 Liquid Biopsies: Circulating Nucleic Acids 2

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作者与单位 Authors & Affiliations

Ekaterina S. Kuligina¹, Aleksandr S. Martianov¹, Liliya S. Baboshkina¹, Arina S. Perevalova¹, Yana V. Belysheva¹, Anastasia N. Ershova¹, Tatiana A. Laidus², Aram A. Musaelyan³, Ekaterina M. Anokhina⁴, Gulfiia M. Teletaeva¹, Aglaya G. Iyevleva¹, Evgeny N. Imyanitov¹

¹N.N. Petrov National Medical Research Center of Oncology, Saint Petersburg, Russian Federation,²Department of Medical Genetics, St.-Petersburg Pediatric Medical University, Saint Petersburg, Russian Federation,³Department of clinical oncology, Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russian Federation,⁴Department of Antitumor Drug Therapy, St. Luke Clinical Hospital, Saint Petersburg, Russian Federation

摘要 Abstract

中文摘要

背景：ctDNA检测的实际应用较为复杂，因为许多肿瘤向血液中释放的DNA量极低。人们已投入大量努力来鉴定影响ctDNA检测性能的因素。最近一项研究证明，在深睡眠阶段（约凌晨4点）循环肿瘤细胞（CTC）数量出现夜间峰值。本研究探讨了同样的峰值是否也是循环肿瘤DNA（ctDNA）的特征。方法：从19例RAS/RAF突变的结直肠癌（CRC）患者采集血浆样本，采集时间为中午12点（第1天）、凌晨4点（夜间）和中午12点（第2天）。14名受试者为本研究提供了单个三联样本，5例患者进行了上述流程两次或三次。血浆中的KRAS、NRAS和BRAF突变通过数字微滴PCR（ddPCR）定量。结果：在25个三联样本中的至少一份血浆样本中，20个（80%）检出RAS/RAF突变（>10拷贝/mL）。其中，15个在所有时间点均可检测到ctDNA，个体内变异范围为1.7%至74.8%。在5个三联样本中，ctDNA在白天不可检测，但在夜间存在。在疾病控制期间采集的9个三联样本中，有7个出现夜间ctDNA峰值，而在肿瘤进展期间获得的全部10个三联样本均显示其他时间模式（p = 0.005，Fisher精确检验）。多次采样的患者依疾病状态显示出不同的ctDNA波动模式。结论：ctDNA水平表现出昼夜变化，在疾病控制的患者中观察到凌晨4点峰值。该结果与先前关于乳腺癌患者CTC夜间激增的报道一致，并提示液体活检结果受昼夜节律或睡眠相关生理变化的调节。这项工作得到俄罗斯科学基金会（资助编号25-45-01051）的支持。

查看英文原文 English abstract

Background: Practical use of ctDNA tests is complicated because many tumors shed into the bloodstream vanishingly low amounts of DNA. Significant efforts have been invested in the identification of factors that influence the performance of ctDNA assays. A recent study demonstrated a nocturnal peak in the amount of circulating tumor cells (CTC) during the deep sleep phase (~4 a.m.). This study questioned whether the same peak is characteristic of circulating tumor DNA (ctDNA). Methods: Plasma samples were collected from 19 RAS/RAF -mutated colorectal cancer (CRC) patients at 12 p.m. (day 1), 4 a.m. (night), and 12 p.m. (day 2). 14 subjects provided a single triplet for the study, and five patients underwent the above procedure twice or thrice. KRAS, NRAS , and BRAF mutations in plasma were quantified via droplet digital PCR (ddPCR). Results: RAS/RAF mutations (>10 copies/mL) were detected in at least one plasma sample in 20 of 25 (80%) triplets. Among these, 15 showed detectable ctDNA at all time points, with intra-individual variation ranging from 1.7% to 74.8%. In five triplets, ctDNA was undetectable during the daytime but present at night. A nocturnal ctDNA peak occurred in 7 of 9 triplets collected during disease control, while all 10 triplets obtained during tumor progression showed other temporal patterns (p = 0.005, Fisher's exact test). Patients sampled multiple times displayed differing ctDNA fluctuation patterns depending on disease status. Conclusions: ctDNA levels exhibit circadian variation, with a 4 a.m. peak observed in patients with disease control. The results align with prior reports on nocturnal surges in CTC in breast cancer patients and suggest that liquid biopsy results are modulated by circadian or sleep-related physiological changes. This work has been supported by the Russian Science Foundation (grant number 25-45-01051)

利益披露 Disclosure

E. S. Kuligina, None.. A. S. Martianov, None.. L. S. Baboshkina, None.. A. S. Perevalova, None.. Y. V. Belysheva, None.. A. N. Ershova, None.. T. A. Laidus, None.. A. A. Musaelyan, None.. E. M. Anokhina, None.. G. M. Teletaeva, None.. A. G. Iyevleva, None.. E. N. Imyanitov, None.

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