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细胞角蛋白8/18在鉴定非小细胞肺癌患者病变来源的循环肿瘤细胞中的应用。

Utility of CK8/18 in identifying circulating tumor cells derived from lesions in patients with non-small cell lung cancer.

作者信息

Sakai Tetsuya, Onishi Mami, Zenke Yoshitaka, Yamamoto Eri Morita, Ijiri Yuichi, Kawasaki Kana, Kato Fumie, Sugano Tomoko, Maharjan Bishnu Devi, Bhagat Ali Asgar S, Yoshida Tomokazu, Iwanaga Shigeki, Yanagida Masatoshi, Goto Koichi

机构信息

Department of Thoracic Oncology, National Cancer Center Hospital East, Chiba, Japan.

Sysmex Corporation, Kobe, Japan.

出版信息

Transl Lung Cancer Res. 2025 Jun 30;14(6):2100-2112. doi: 10.21037/tlcr-2025-155. Epub 2025 Jun 23.

Abstract

BACKGROUND

Circulating tumor cells (CTCs) are identified by the absence of pan-leukocyte markers and positive staining for cytokeratin (CK). Anti-panCK antibody (AE1/AE3) is a widely used marker for CK. However, epithelial-mesenchymal transition reduces the expression of panCK markers, leading to low detection rates of CTCs, especially in non-small cell lung cancer (NSCLC). This study aimed to evaluate the efficacy of a novel CTC detection system using CK8/18 as an epithelial cell marker in patients with NSCLC.

METHODS

A total of 20 patients with NSCLC (10 mutant and 10 wild-type) were included in this study. Blood samples were examined using the novel CTC detection system. Both anti-panCK and anti-CK8/18 antibodies were used to identify CK and detect CTCs. Additionally, CTCs isolated from patients with mutations underwent single-cell sorting, whole genome amplification, and gene analysis to verify their lung cancer origin.

RESULTS

CTCs were detected in 17 patients (8 mutant and 9 wild-type) using CK8/18 and in only 8 patients (5 mutant and 3 wild-type) using panCK. The sensitivity of CTC detection based on CK8/18 was significantly higher than that based on panCK (85% 40%, P<0.01). Among the 10 patients with mutations, mutations were confirmed in CTCs obtained from six patients in the gene analysis through single-cell sorting, aligning with mutations identified in tissue samples.

CONCLUSIONS

This study demonstrated the effectiveness of CK8/18 over panCK in detecting CTCs. Adopting CK8/18 in the novel system improved the detection rate of CTCs, highlighting its potential in clinical applications.

摘要

背景

循环肿瘤细胞(CTCs)通过缺乏全白细胞标志物和细胞角蛋白(CK)阳性染色来识别。抗全细胞角蛋白抗体(AE1/AE3)是一种广泛使用的CK标志物。然而,上皮-间质转化会降低全细胞角蛋白标志物的表达,导致CTCs的检测率较低,尤其是在非小细胞肺癌(NSCLC)中。本研究旨在评估一种以CK8/18作为上皮细胞标志物的新型CTCs检测系统在NSCLC患者中的疗效。

方法

本研究共纳入20例NSCLC患者(10例突变型和10例野生型)。使用新型CTCs检测系统对血样进行检测。抗全细胞角蛋白抗体和抗CK8/18抗体均用于识别CK并检测CTCs。此外,对从突变患者中分离出的CTCs进行单细胞分选、全基因组扩增和基因分析,以验证其肺癌起源。

结果

使用CK8/18在17例患者(8例突变型和9例野生型)中检测到CTCs,而使用全细胞角蛋白仅在8例患者(5例突变型和3例野生型)中检测到CTCs。基于CK8/18的CTCs检测灵敏度显著高于基于全细胞角蛋白的检测灵敏度(85%对40%,P<0.01)。在10例有突变的患者中,通过单细胞分选在基因分析中从6例患者获得的CTCs中确认了突变,与组织样本中鉴定的突变一致。

结论

本研究证明了CK8/18在检测CTCs方面优于全细胞角蛋白。在新型系统中采用CK8/18提高了CTCs的检测率,突出了其在临床应用中的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fa2/12261347/cba9ec32b245/tlcr-14-06-2100-f1.jpg

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