Detection of Circulating Tumor Cells in Lung Cancer Patients with Antibody Immune Lipid Magnetic Particles_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

XiaoHua ^1# , ChenSi ^1# , ZhangWei ¹ , LuChengjun ² , LiangXiaofei ³ , ShenHebai ³ , JinHai ² ,  WuJunjie ¹ ,  LiQiang ¹

1. Department of Respiratory and Critical Care Medicine, Changhai Hospital of Shanghai, The Second Military Medical University, Shanghai, 200433, China;
2. ;
3. ;

Corresponding author：

WuJunjie, Email: wjjxcc@126.com; LiQiang, Email: liqressh@hotmail.com

Keywords：

Lung cancer; Circulating tumor cells; Epithelial cell adhesion molecule; Epidermal growth factor receptor; Immune magnetic particles

DOI：

10.7507/1671-6205.2016035

Video：

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Objective To assess the efficacy of a kind of new material lipid magnetic particle for isolation and detection of lung cancer circulating tumor cells (CTCs). Methods Immune lipid magnetic particles were prepared with reverse evaporation method and they were assembled into kits with EpCAM and EGFR antibody respectively. Their efficacy were evaluated by detecting A549 cells in group A (A549 cells mixed in phosphated buffer solution) and group B (A549 cells mixed in blood from healthy volunteers). Lung cancer CTCs of hospitalized patients were also detected with both immune magnetic particals. Then the detecting efficacy was compared between EpCAM immune lipid magnetic particles and the conventional Cellsearch^TM system. Results The immune lipid magnetic particles had high capture efficiency for CTCs isolation and identification. The median of EpCAM immune lipid magnetic particles method in detecting A549 cells in group A was 92%, and EGFR was 90%. The median of EpCAM immune lipid magnetic particles method in detecting A549 cells in group B was 85%, and EGFR was 81%. In 13 patients with lung cancer, CTCs can be detected with both immune lipid magnetic particles methods and both medians were 5; In negative control, the medians of both methods were 0 (P＜0.05). EpCAM immune lipid magnetic particles method can detect more CTCs than conventional Cellsearch^TM system in 3 lung cancer patients. Conclusions Immune lipid magnetic particles have good efficacy for lung cancer CTCs detection and has promising clinical application value. The EpCAM immune lipid magnetic particles have equal efficiency in detecting lung cancer CTCs with EGFR. There is a trend that EpCAM immune lipid magnetic particles is superior to the conventional Cellsearch^TM system.

Citation： XiaoHua, ChenSi, ZhangWei, LuChengjun, LiangXiaofei, ShenHebai, JinHai, WuJunjie, LiQiang. Detection of Circulating Tumor Cells in Lung Cancer Patients with Antibody Immune Lipid Magnetic Particles. Chinese Journal of Respiratory and Critical Care Medicine, 2016, 15(2): 147-152. doi: 10.7507/1671-6205.2016035 Copy

1.	Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin, 2015, 65:87-108.
2.	Galanzha EI, Shashkov EV, Kelly T, et al. In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells. Nat Nanotechnol, 2009, 4:855-860.
3.	Ghazani AA, Castro CM, Gorbatov R, et al. Sensitive and direct detection of circulating tumor cells by multimarker μ-nuclear magnetic resonance. Neoplasia, 2012, 14:388-395. 388-IN382.
4.	欧兆荣, 陶连琴, 时国朝, 等.孤立性肺结节的影像学特征及两种肺癌预测模型的比较.中国呼吸与危重监护杂志, 2012, 11:168-171.
5.	Beije N, Jager A, Sleijfer S. Circulating tumor cell enumeration by the CellSearch system: the clinician’s guide to breast cancer treatment? Cancer Treat Rev, 2015, 41:144-150.
6.	Ilie M, Hofman V, Long E, et al. Current challenges for detection of circulating tumor cells and cell-free circulating nucleic acids, and their characterization in non-small cell lung carcinoma patients. What is the best blood substrate for personalized medicine? Ann Transl Med, 2014, 2:107.
7.	Liang XF, Wang HJ, Luo H, et al.Characterization of novel multifunctional cationic polymeric liposomes formed from octadecyl quaternized carboxymethyl chitosan/cholesterol and drug encapsulation. Langmuir, 2008, 24:7147-7153.
8.	Liang XF, Wang HJ, Jiang XG, et al.Development of monodispersed and functional magnetic nanospheres via simple liposome method.J Nanoparticle Res, 2010, 12:1723-1732.
9.	梁晓飞, 王汉杰, 田惠, 等.载药磁性阳离子高聚物脂质体的制备及表征.高等学校化学学报, 2008, 28:858-861.
10.	Alix-Panabieres C, Pantel K.Technologies for detection of circulating tumor cells:facts and vision.Lab on a chip, 2014, 14:57-62.
11.	Wang ST, Liu K, Liu J, et al. Highly efficient capture of circulating tumor cells using nanostructured silicon substrates with integrated chaotic micromixers Angew Chem Int Ed Engl, 2011, 50:3084-3088.
12.	张浩, 任秀红, 刘莉.PD-L1和EGFR在非小细胞肺癌组织中的表达及相关性分析.疑难病杂志, 2015, 14:786-792.
13.	Ashworth TR.A case of cancer in which cells similar to those in the tumors were seen in the blood after death.Aust Med J, 1869, 14:146-149.
14.	Huang CH, Wick JA, Sittampalam GS, et al.A multicenter pilot study examining the role of circulating tumor cells as a blood-based tumor marker in patients with extensive small-cell lung cancer.Front Oncol, 2014, 4:1-7.
15.	Chang CL, Huang W, Jalal SI, et al.Circulating tumor cell detection using a parallel flow micro-aperture chip system.Lab on a chip, 2015, 15:1677-1688.
16.	Goldkorn A, Ely B, Quinn I, et al. Circulating tumor cell counts are prognostic of overall survival in SWOG S0421: a phase Ⅲ trial of docetaxel with or without atrasentan for metastatic castration-resistant prostate cancer. J Clin Oncol, 2014, 32:1136-1142.
17.	Lucci A, Hall CS, Lodhi AK, et al.Circulating tumour cells in non-metastatic breast cancer:a prospective study.Lancet Oncol, 2012,13:688-695.

1. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin, 2015, 65:87-108.
2. Galanzha EI, Shashkov EV, Kelly T, et al. In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells. Nat Nanotechnol, 2009, 4:855-860.
3. Ghazani AA, Castro CM, Gorbatov R, et al. Sensitive and direct detection of circulating tumor cells by multimarker μ-nuclear magnetic resonance. Neoplasia, 2012, 14:388-395. 388-IN382.
4. 欧兆荣, 陶连琴, 时国朝, 等.孤立性肺结节的影像学特征及两种肺癌预测模型的比较.中国呼吸与危重监护杂志, 2012, 11:168-171.
5. Beije N, Jager A, Sleijfer S. Circulating tumor cell enumeration by the CellSearch system: the clinician’s guide to breast cancer treatment? Cancer Treat Rev, 2015, 41:144-150.
6. Ilie M, Hofman V, Long E, et al. Current challenges for detection of circulating tumor cells and cell-free circulating nucleic acids, and their characterization in non-small cell lung carcinoma patients. What is the best blood substrate for personalized medicine? Ann Transl Med, 2014, 2:107.
7. Liang XF, Wang HJ, Luo H, et al.Characterization of novel multifunctional cationic polymeric liposomes formed from octadecyl quaternized carboxymethyl chitosan/cholesterol and drug encapsulation. Langmuir, 2008, 24:7147-7153.
8. Liang XF, Wang HJ, Jiang XG, et al.Development of monodispersed and functional magnetic nanospheres via simple liposome method.J Nanoparticle Res, 2010, 12:1723-1732.
9. 梁晓飞, 王汉杰, 田惠, 等.载药磁性阳离子高聚物脂质体的制备及表征.高等学校化学学报, 2008, 28:858-861.
10. Alix-Panabieres C, Pantel K.Technologies for detection of circulating tumor cells:facts and vision.Lab on a chip, 2014, 14:57-62.
11. Wang ST, Liu K, Liu J, et al. Highly efficient capture of circulating tumor cells using nanostructured silicon substrates with integrated chaotic micromixers Angew Chem Int Ed Engl, 2011, 50:3084-3088.
12. 张浩, 任秀红, 刘莉.PD-L1和EGFR在非小细胞肺癌组织中的表达及相关性分析.疑难病杂志, 2015, 14:786-792.
13. Ashworth TR.A case of cancer in which cells similar to those in the tumors were seen in the blood after death.Aust Med J, 1869, 14:146-149.
14. Huang CH, Wick JA, Sittampalam GS, et al.A multicenter pilot study examining the role of circulating tumor cells as a blood-based tumor marker in patients with extensive small-cell lung cancer.Front Oncol, 2014, 4:1-7.
15. Chang CL, Huang W, Jalal SI, et al.Circulating tumor cell detection using a parallel flow micro-aperture chip system.Lab on a chip, 2015, 15:1677-1688.
16. Goldkorn A, Ely B, Quinn I, et al. Circulating tumor cell counts are prognostic of overall survival in SWOG S0421: a phase Ⅲ trial of docetaxel with or without atrasentan for metastatic castration-resistant prostate cancer. J Clin Oncol, 2014, 32:1136-1142.
17. Lucci A, Hall CS, Lodhi AK, et al.Circulating tumour cells in non-metastatic breast cancer:a prospective study.Lancet Oncol, 2012,13:688-695.

Chinese Journal of Respiratory and Critical Care Medicine

Detection of Circulating Tumor Cells in Lung Cancer Patients with Antibody Immune Lipid Magnetic Particles

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