PO.CL01.23 · 临床研究
通过循环癌症干细胞监测结直肠癌患者的肿瘤动态
Monitoring tumor dynamics through circulating cancer stem cells in colorectal cancer patients
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：
结直肠癌（CRC）仍是全球最常被诊断且最致命的恶性肿瘤之一。肿瘤复发和转移是决定患者生存的主要因素。循环癌症干细胞（cCSCs）是存在于外周血中的一种罕见肿瘤细胞亚群，被认为可驱动肿瘤生长、转移和治疗耐药。虽然肿瘤球（tumorsphere）培养已被用于从原发肿瘤或细胞系中鉴定癌症干细胞，但我们已建立了一种在CRC患者血液中检测和表征循环癌症干细胞的有效方法。
方法：
本研究纳入了转移性和非转移性CRC患者。为检测循环癌症干细胞，我们采用了肿瘤球形成的功能性检测（stemtrac®）。使用免疫荧光和qRT-PCR评估表面标志物表达和多能性相关基因。此外，我们报道了一例40岁男性转移性KRAS阳性CRC患者的病例，通过循环上皮肿瘤细胞（CETCs/CTCs）和cCSC分析对其进行了纵向监测，并与临床和影像学结果相关联。
结果：
与非转移性患者相比，转移性疾病患者表现出显著更多的肿瘤球数量（中位数：每100 µl血液48个对比15个球），提示肿瘤球计数与疾病分期之间存在相关性。肿瘤球表现出EpCAM和CD133的高表达、ALDH1活性升高，以及SOX2、OCT4和NANOG等多能性基因的上调。在健康对照中未观察到球形成（n = 50）。在该病例研究中，CETCs/CTCs和cCSC水平的波动反映了治疗反应和疾病活动，其持续升高先于疾病进展的临床或影像学证据出现。
结论：
本研究表明，可从转移性和非转移性CRC患者的外周血中检测到肿瘤干细胞。源自循环癌症干细胞的肿瘤球数量可作为转移潜能的独立指标。对CETCs/CTCs和cCSCs的连续监测提供了一种非侵入性和动态的工具，用于评估治疗疗效和识别早期疾病进展。更深入地理解循环癌症干细胞的生物学特性可能有助于为结直肠癌开发更有效和个性化的治疗策略。
查看英文原文 English abstract
Background:
Colorectal cancer (CRC) remains one of the most commonly diagnosed and lethal malignancies worldwide. Tumor recurrence and metastasis are major determinants of patient survival. Circulating cancer stem cells (cCSCs), a rare subpopulation of tumor cells present in peripheral blood, are believed to drive tumor growth, metastasis, and therapy resistance. While tumorsphere culture has been used to identify cancer stem cells from primary tumors or cell lines, we have established an effective method for detecting and characterizing circulating cancer stem cells in the blood of CRC patients.
Methods:
Metastatic and non-metastatic CRC patients were included in this study. For the detection of circulating cancer stem cells, we used a functional assay for tumorsphere formation (stemtrac®). Immunofluorescence and qRT-PCR were employed to assess surface marker expression and pluripotency-associated genes. Additionally, we report a case of a 40-year-old man with metastatic KRAS-positive CRC, who was longitudinally monitored using both circulating epithelial tumor cell (CETCs/CTCs) and cCSC analyses in correlation with clinical and imaging findings.
Results:
Patients with metastatic disease exhibited a significantly higher number of tumorspheres compared with non-metastatic patients (median: 48 vs. 15 spheres per 100 µl blood), suggesting a correlation between tumorsphere count and disease stage. Tumorspheres showed high expression of EpCAM and CD133, elevated ALDH1 activity, and upregulation of pluripotency genes such as SOX2, OCT4, and NANOG. No sphere formation was observed in healthy controls (n = 50). In the case study, fluctuations in CETCs/CTCs and cCSC levels reflected treatment response and disease activity, with sustained increases preceding clinical or radiological evidence of progression.
Conclusion:
This study demonstrates that tumor stem cells can be detected in peripheral blood from both metastatic and non-metastatic CRC patients. The number of tumorspheres derived from circulating cancer stem cells serves as an independent indicator of metastatic potential. Serial monitoring of CETCs/CTCs and cCSCs provides a non-invasive and dynamic tool for evaluating treatment efficacy and identifying early disease progression. A deeper understanding of the biology of circulating cancer stem cells may facilitate the development of more effective and personalized therapeutic strategies for colorectal cancer.
利益披露 Disclosure
M. Pizon, None..
D. Schott, None..
U. Pachmann, None..
K. Pachmann, None.