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细胞外囊泡相关表皮生长因子受体作为肺腺癌潜在的液体活检生物标志物:一项病例对照研究

Extracellular vesicle-associated epidermal growth factor receptor as a potential liquid biopsy biomarker in lung adenocarcinoma: a case-control study.

作者信息

Salih Dian Jamel

机构信息

Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.

Department of Anatomy, Biology and Histology, College of Medicine, University of Duhok, Duhok, Iraq.

出版信息

J Yeungnam Med Sci. 2025;42:36. doi: 10.12701/jyms.2025.42.36. Epub 2025 May 23.

Abstract

BACKGROUND

Extracellular vesicles (EVs) have recently emerged as potential noninvasive biomarkers for liquid biopsy because of the limitations of tissue biopsies in lung cancer. This study investigated the presence of EV-associated epidermal growth factor receptor (EGFR) in lung adenocarcinoma.

METHODS

EVs were collected from the serum samples of 32 patients with lung adenocarcinoma, 32 healthy controls, and conditioned culture media from A549 and BEAS-2B cell lines. EVs were isolated using ultracentrifugation and size-exclusion chromatography. Their characteristic features were confirmed by transmission electron microscopy, nanoparticle tracking analysis (NTA), and western blotting.

RESULTS

NTA revealed a two-fold increase in EV concentration in the serum of patients with lung cancer compared to healthy controls. Similarly, A549 cells secrete significantly more EVs than BEAS-2B cells. Western blotting validated the detection of canonical EV markers, such as TSG101, CD81, and flotillin-1, as well as the absence of calnexin. Notably, EGFR was highly packaged in the EVs isolated from both A549 cells and patient serum, whereas it was minimally present or absent in the EVs isolated from healthy controls and BEAS-2B cells.

CONCLUSION

Our findings indicated that EGFR was selectively packaged into EVs derived from lung adenocarcinoma and was absent in non-cancerous controls. EV-associated EGFR could be a noninvasive indicator for the early detection of lung adenocarcinoma through liquid biopsy.

摘要

背景

由于组织活检在肺癌诊断中存在局限性,细胞外囊泡(EVs)最近已成为液体活检潜在的非侵入性生物标志物。本研究调查了肺腺癌中与EV相关的表皮生长因子受体(EGFR)的存在情况。

方法

从32例肺腺癌患者的血清样本、32例健康对照以及A549和BEAS-2B细胞系的条件培养基中收集EVs。使用超速离心和尺寸排阻色谱法分离EVs。通过透射电子显微镜、纳米颗粒跟踪分析(NTA)和蛋白质印迹法确认其特征。

结果

NTA显示,与健康对照相比,肺癌患者血清中EV浓度增加了两倍。同样,A549细胞分泌的EVs明显多于BEAS-2B细胞。蛋白质印迹法验证了典型EV标志物(如TSG101、CD81和flotillin-1)的检测,以及钙连接蛋白的缺失。值得注意的是,EGFR高度包裹在从A549细胞和患者血清中分离的EVs中,而在从健康对照和BEAS-2B细胞中分离的EVs中含量极少或不存在。

结论

我们的研究结果表明,EGFR被选择性地包裹在源自肺腺癌的EVs中,而在非癌对照中不存在。与EV相关的EGFR可能是通过液体活检早期检测肺腺癌的非侵入性指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e75d/12303782/922302a6167b/jyms-2025-42-36f1.jpg

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