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监测晚期 EGFR 突变型非小细胞肺癌患者中存在的波形蛋白阳性循环肿瘤干细胞和肿瘤细胞的水平。

Monitoring levels of vimentin-positive circulating cancer stem cells and tumor cells in patients with advanced EGFR-mutated non-small cell lung cancer.

机构信息

Division of Pulmonary Medicine, Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.

Division of Pulmonary Medicine, Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taiwan.

出版信息

Lung Cancer. 2021 Jun;156:50-58. doi: 10.1016/j.lungcan.2021.04.014. Epub 2021 Apr 18.

Abstract

OBJECTIVES

Circulating tumor cells (CTCs) are associated with tumor spread, whereas cancer stem cells may be related to drug resistance. However, few studies have analyzed the levels of circulating cancer stem cells (CCSCs) and CTCs in patients with advanced non-small cell lung cancer (NSCLC).

MATERIALS AND METHODS

Treatment-naïve patients with EGFR-mutated NSCLC who received epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy were recruited prospectively. The cell surface vimentin antibody was used for CTC detection and CD133 antibody for CCSC detection. CCSC and CTC levels were measured as cell count per 4 mL of blood, before treatment, after 2 and 12 weeks of treatment, and at disease progression. Data on clinical characteristics and outcomes were also collected.

RESULTS

At diagnosis (n = 29), the median CCSC and CTC levels were 0 (interquartile range, 0-2) and 3 (2-9), respectively. After 12 weeks, the CCSC and CTC levels were lower than those at diagnosis (CCSC: 0 (0-0), p = 0.14; CTC: 1 (0-4), p = 0.048). At disease progression, the median CCSC and CTC levels were 0 (0-1) and 1 (0-2), respectively. Patients with higher CCSC and CTC levels at diagnosis had a numerically shorter progression-free survival.

CONCLUSION

In patients with EGFR-mutated NSCLC, CCSC and CTC levels became lower after 12 weeks of EGFR-TKI therapy and remained low at disease progression. High pre-treatment CCSC and CTC levels may be associated with a trend towards poor treatment outcomes.

摘要

目的

循环肿瘤细胞(CTCs)与肿瘤扩散有关,而癌症干细胞可能与耐药性有关。然而,很少有研究分析晚期非小细胞肺癌(NSCLC)患者循环肿瘤干细胞(CCSCs)和 CTCs 的水平。

材料和方法

前瞻性招募了接受表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)治疗的 EGFR 突变型 NSCLC 初治患者。使用细胞表面波形蛋白抗体检测 CTC,使用 CD133 抗体检测 CCSC。在治疗前、治疗后 2 周和 12 周以及疾病进展时,以每 4 毫升血液的细胞数测量 CCSC 和 CTC 水平。还收集了临床特征和结局的数据。

结果

在诊断时(n=29),CCSC 和 CTC 的中位数水平分别为 0(四分位距,0-2)和 3(2-9)。治疗 12 周后,CCSC 和 CTC 水平低于诊断时(CCSC:0(0-0),p=0.14;CTC:1(0-4),p=0.048)。疾病进展时,CCSC 和 CTC 的中位数水平分别为 0(0-1)和 1(0-2)。诊断时 CCSC 和 CTC 水平较高的患者无进展生存期较短。

结论

在 EGFR 突变型 NSCLC 患者中,EGFR-TKI 治疗 12 周后 CCSC 和 CTC 水平降低,疾病进展时仍保持较低水平。治疗前 CCSC 和 CTC 水平较高可能与治疗结局较差的趋势相关。

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