Value of polypeptide-based nanomagnetic circulating tumor cells detection for the differential diagnosis of pulmonary nodules_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

LI Kaidi ¹ ,  LIANG Naixin ¹ , LIU Hongsheng ¹ , LI Li ¹ , HUANG Cheng ¹ , QIN Yingzhi ¹ , HAN Zhijun ¹ , BING Zhongxing ¹ , LIU Lei ¹ , XU Yuan ¹ , XU Huihui ² , YANG Yanlian ² , PENG Jiaxi ² , HUO Li ³ , LI Fang ³ , HU Zhiyuan ² ,  LI Shanqing ¹

1. Department of Thoracic Surgery, Peking Union Medical College Hospital, CAMS & PUMC, Beijing, 100730, P.R.China;
2. National Center for Nanoscience and Technology, Beijing, 100190, P.R.China;
3. Department of Nuclear Medicine, Peking Union Medical College Hospital, CAMS & PUMC, Beijing, 100730, P.R.China;

Corresponding author：

LIANG Naixin, Email: liangnaixin@pumch.cn; LI Shanqing, Email: lishanqing2016@cntv.cn

Keywords：

Pulmonary nodules; differential diagnosis; diagnostic tests; liquid biopsy; circulating tumor cells

DOI：

10.7507/1007-4848.201708060

Video：

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Objective To explore the efficacy of a novel detection technique of circulating tumor cells (CTCs) to identify benign and malignant lung nodules. Methods Nanomagnetic CTC detection based on polypeptide with epithelial cell adhesion molecule (EpCAM)-specific recognition was performed on enrolled patients with pulmonary nodules. There were 73 patients including 48 patients with malignant lesions as a malignant group and 25 patients with benign lesion as a benign group. There were 13 males and 35 females at age of 57.0±11.9 years in the malignant group and 11 males and 14 females at age of 53.1±13.2 years in the benign group. e calculated the differential diagnostic efficacy of CTC count, and conducted subgroup analysis according to the consolidation-tumor ratio, while compared with PET/CT on the efficacy. Results CTC count of the malignant group was significantly higher than that of the benign group (0.50/ml vs. 0.00/ml, P<0.05). Subgroup analysis according to consolidation tumor ratio (CTR) revealed that the difference was statistically significant in pure ground glass (pGGO) nodules 1.00/mlvs. 0.00/ml, P<0.05), but not in part-solid or pure solid nodules. For pGGO nodules, the area under the receiver operating characteristic (ROC) curve of CTC count was 0.833, which was significantly higher than that of maximum of standardized uptake value (SUVmax) (P<0.001). Its sensitivity and specificity was 80.0% and 83.3%, respectively. Conclusion The peptide-based nanomagnetic CTC detection system can differentiate malignant tumor and benign lesions in pulmonary nodules presented as pGGO. It is of great clinical potential as a noninvasive, nonradiating method to identify malignancies in pulmonary nodules.

Citation： LI Kaidi, LIANG Naixin, LIU Hongsheng, LI Li, HUANG Cheng, QIN Yingzhi, HAN Zhijun, BING Zhongxing, LIU Lei, XU Yuan, XU Huihui, YANG Yanlian, PENG Jiaxi, HUO Li, LI Fang, HU Zhiyuan, LI Shanqing. Value of polypeptide-based nanomagnetic circulating tumor cells detection for the differential diagnosis of pulmonary nodules. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2018, 25(7): 560-566. doi: 10.7507/1007-4848.201708060 Copy

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12.	Subedi N, Scarsbrook A, Darby M, et al. The clinical impact of integrated FDG PET-CT on management decisions in patients with lung cancer. Lung Cancer, 2009, 64(3): 301-307.
13.	Bryant AS, Cerfolio RJ. The maximum standardized uptake values on integrated FDG-PET/CT is useful in differentiating benign from malignant pulmonary nodules. Ann Thorac Surg, 2006, 82(3): 1016-1020.
14.	Bunyaviroch T, Coleman RE. PET evaluation of lung cancer. J Nucl Med, 2006, 47(3): 451-469.
15.	Xiu Y, Bhutani C, Dhurairaj T, et al. Dual-time point FDG PET imaging in the evaluation of pulmonary nodules with minimally increased metabolic activity. Clin Nucl Med, 2007, 32(2): 101-105.
16.	Nomori H, Watanabe K, Ohtsuka T, et al. Evaluation of F-18 fluorodeoxyglucose (FDG) PET scanning for pulmonary nodules less than 3 cm in diameter, with special reference to the CT images. Lung Cancer, 2004, 45(1): 19-27.
17.	Nomori H, Watanabe K, Ohtsuka T, et al. Visual and semiquantitative analyses for F-18 fluorodeoxyglucose PET scanning in pulmonary nodules 1 cm to 3 cm in size. Ann Thorac Surg, 2005, 79(3): 984-988.
18.	Wan JW, Gao MZ, Hu RJ, et al. A preliminary study on the relationship between circulating tumor cells count and clinical features in patients with non-small cell lung cancer. Ann Transl Med, 2015, 3(22): 352.
19.	Chen X, Wang X, He H, et al. Combination of circulating tumor cells with serum carcinoembryonic antigen enhances clinical prediction of non-small cell lung cancer. PLoS One, 2015, 10(5): e0126276.
20.	Shi Y, Wu H, Zhang M, et al. Expression of the epithelial-mesenchymal transition-related proteins and their clinical significance in lung adenocarcinoma. Diagn Pathol, 2013, 8: 89.
21.	Chen D, Zhang Y, Zhang X, et al. Overexpression of integrin-linked kinase correlates with malignant phenotype in non-small cell lung cancer and promotes lung cancer cell invasion and migration via regulating epithelial-mesenchymal transition (EMT)-related genes. Acta Histochem, 2013, 115(2): 128-136.
22.	Krebs MG, Hou JM, Sloane R, et al. Analysis of circulating tumor cells in patients with non-small cell lung cancer using epithelial marker-dependent and -independent approaches. J Thorac Oncol, 2012, 7(2): 306-315.
23.	Singh A, Settleman J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene, 2010, 29(34): 4741-4751.
24.	Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer, 2002, 2(6): 442-454.
25.	Gorges TM, Tinhofer I, Drosch M, et al. Circulating tumour cells escape from EpCAM-based detection due to epithelial-to-mesenchymal transition. BMC Cancer, 2012, 12: 178.

1. Siegel R, Ma J, Zou Z, et al. Cancer statistics, 2014. CA Cancer J Clin, 2014, 64(1): 9-29.
2. Zeng H, Zheng R, Guo Y, et al. Cancer survival in China, 2003-2005: a population-based study. Int J Cancer, 2015, 136(8): 1921-1930.
3. National Lung Screening Trial Research Team, Aberle DR, Adams AM, Berg CD, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med, 2011, 365(5): 395-409.
4. 周清华, 范亚光, 王颖, 等. 中国肺部结节分类、诊断与治疗指南(2016 年版). 中国肺癌杂志, 2016, 19(12): 793-798.
5. Zhang L, Li L, Li H, et al.[Clinical significance of tumor markers in the diagnosis of lung cancer]. Zhongguo Fei Ai Za Zhi, 2002, 5(3): 214-216.
6. Ung YC, Maziak DE, Vanderveen JA, et al. 18F fluorodeoxy glucose positron emission tomography in the diagnosis and staging of lung cancer: a systematic review. J Natl Cancer Inst, 2007, 99(23): 1753-1767.
7. Tanaka F, Yoneda K, Kondo N, et al. Circulating tumor cell as a diagnostic marker in primary lung cancer. Clin Cancer Res, 2009, 15(22): 6980-6986.
8. Bai L, Du Y, Peng J, et al. Peptide-based isolation of circulating tumor cells by magnetic nanoparticles. J Mater Chem B, 2014, 2(26): 4080-4088.
9. Liu XR, Shao B, Peng JX, et al. Identification of high independent prognostic value of nanotechnology based circulating tumor cell enumeration in first-line chemotherapy for metastatic breast cancer patients. Breast, 2017, 32: 119-125.
10. Hansell DM, Bankier AA, Macmahon H, et al. Fleischner Society: glossary of terms for thoracic imaging. Radiology, 2008, 246(3): 697-722.
11. Hattori A, Matsunaga T, Hayashi T, et al. Prognostic impact of the findings on thin-section computed tomography in patients with subcentimeter non-small cell lung cancer. J Thorac Oncol, 2017, 12(6): 954-962.
12. Subedi N, Scarsbrook A, Darby M, et al. The clinical impact of integrated FDG PET-CT on management decisions in patients with lung cancer. Lung Cancer, 2009, 64(3): 301-307.
13. Bryant AS, Cerfolio RJ. The maximum standardized uptake values on integrated FDG-PET/CT is useful in differentiating benign from malignant pulmonary nodules. Ann Thorac Surg, 2006, 82(3): 1016-1020.
14. Bunyaviroch T, Coleman RE. PET evaluation of lung cancer. J Nucl Med, 2006, 47(3): 451-469.
15. Xiu Y, Bhutani C, Dhurairaj T, et al. Dual-time point FDG PET imaging in the evaluation of pulmonary nodules with minimally increased metabolic activity. Clin Nucl Med, 2007, 32(2): 101-105.
16. Nomori H, Watanabe K, Ohtsuka T, et al. Evaluation of F-18 fluorodeoxyglucose (FDG) PET scanning for pulmonary nodules less than 3 cm in diameter, with special reference to the CT images. Lung Cancer, 2004, 45(1): 19-27.
17. Nomori H, Watanabe K, Ohtsuka T, et al. Visual and semiquantitative analyses for F-18 fluorodeoxyglucose PET scanning in pulmonary nodules 1 cm to 3 cm in size. Ann Thorac Surg, 2005, 79(3): 984-988.
18. Wan JW, Gao MZ, Hu RJ, et al. A preliminary study on the relationship between circulating tumor cells count and clinical features in patients with non-small cell lung cancer. Ann Transl Med, 2015, 3(22): 352.
19. Chen X, Wang X, He H, et al. Combination of circulating tumor cells with serum carcinoembryonic antigen enhances clinical prediction of non-small cell lung cancer. PLoS One, 2015, 10(5): e0126276.
20. Shi Y, Wu H, Zhang M, et al. Expression of the epithelial-mesenchymal transition-related proteins and their clinical significance in lung adenocarcinoma. Diagn Pathol, 2013, 8: 89.
21. Chen D, Zhang Y, Zhang X, et al. Overexpression of integrin-linked kinase correlates with malignant phenotype in non-small cell lung cancer and promotes lung cancer cell invasion and migration via regulating epithelial-mesenchymal transition (EMT)-related genes. Acta Histochem, 2013, 115(2): 128-136.
22. Krebs MG, Hou JM, Sloane R, et al. Analysis of circulating tumor cells in patients with non-small cell lung cancer using epithelial marker-dependent and -independent approaches. J Thorac Oncol, 2012, 7(2): 306-315.
23. Singh A, Settleman J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene, 2010, 29(34): 4741-4751.
24. Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer, 2002, 2(6): 442-454.
25. Gorges TM, Tinhofer I, Drosch M, et al. Circulating tumour cells escape from EpCAM-based detection due to epithelial-to-mesenchymal transition. BMC Cancer, 2012, 12: 178.

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