Detection of circulating tumor cells in patients with lung cancer using metallic micro‑cavity array filter: A pilot study

Ichimura,Hideo; Nawa,Takeshi; Yamamoto,Yusuke; Shimizu,Kei; Kobayashi,Keisuke; Kitazawa,Shinsuke; Kanbara,Hisashige; Odagiri,Taihei; Endo,Katsuya; Matsunaga,Tatsuya; Nakamura,Seita; Yagi,Satomi; Sato,Yukio

doi:10.3892/mco.2020.1973

Detection of circulating tumor cells in patients with lung cancer using metallic micro‑cavity array filter: A pilot study

Authors:
- Hideo Ichimura
- Takeshi Nawa
- Yusuke Yamamoto
- Kei Shimizu
- Keisuke Kobayashi
- Shinsuke Kitazawa
- Hisashige Kanbara
- Taihei Odagiri
- Katsuya Endo
- Tatsuya Matsunaga
- Seita Nakamura
- Satomi Yagi
- Yukio Sato
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Affiliations: Department of Thoracic Surgery, Hitachi General Hospital, Hitachi, Ibaraki 317‑0077, Japan, Department of Respiratory Medicine, Hitachi General Hospital, Hitachi, Ibaraki 317‑0077, Japan, Life Science Business Headquaters, Hitachi Chemical Co., Ltd., Chikusei, Ibaraki 308‑0861, Japan, Department of Thoracic Surgery, University of Tsukuba, Tsukuba, Ibaraki 305‑8575, Japan
Published online on: January 10, 2020 https://doi.org/10.3892/mco.2020.1973
Pages: 278-283

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Abstract

We have developed a metallic micro‑cavity array filter and an automated detection system for capturing circulating tumor cells (CTCs). In this single institutional pilot study, we assessed the ability of this device to detect CTCs in patients with lung cancer at each stage. Patients diagnosed with lung cancer, undergoing planned surgery for lung cancer, or suspected of having lung cancer were recruited (40 recruited and 2 excluded). Blood samples were obtained from the patients and 3 ml whole blood was applied to the device without any preparation. The captured cells were stained to differentiate the nucleus, and determine cytokeratin and CD45 expression. Subsequently, two operators blinded to clinical information counted the number of CTCs. Sample collection was performed at the time of recruitment, before treatment and ~3 months after initial blood collection. CTC counts at recruitment were 1.4±0.4, 1.8±1.2, 1.3±0.6 and 7.4±5.1 (mean ± SE) in clinical stages I, II, III and IV, respectively. No significant difference was observed among the stages. These data indicated the ability of this device to detect CTCs at early or non‑metastatic stages of lung cancer. Further research on a larger scale is needed for a more accurate assessment of the device, and research on the utility of captured cells remains a future challenge.

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1	Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018.PubMed/NCBI View Article : Google Scholar
2	Cufari ME, Proli C, De Sousa P, Raubenheimer H, Al Sahaf M, Chavan H, Shedden L, Niwaz Z, Leung M, Nicholson AG, et al: Increasing frequency of non-smoking lung cancer: Presentation of patients with early disease to a tertiary institution in the UK. Eur J Cancer. 84:55–59. 2017.PubMed/NCBI View Article : Google Scholar
3	Sawabata N, Asamura H, Goya T, Mori M, Nakanishi Y, Eguchi K, Koshiishi Y, Okumura M, Miyaoka E and Fujii Y: Japanese Joint Committee for Lung Cancer Registry: Japanese Lung Cancer Registry Study: First prospective enrollment of a large number of surgical and nonsurgical cases in 2002. J Thorac Oncol. 5:1369–1375. 2010.PubMed/NCBI View Article : Google Scholar
4	Rosell R, Bivona TG and Karachaliou N: Genetics and biomarkers in personalisation of lung cancer treatment. Lancet. 382:720–731. 2013.PubMed/NCBI View Article : Google Scholar
5	Lindeman NI, Cagle PT, Aisner DL, Arcila ME, Beasley MB, Bernicker EH, Colasacco C, Dacic S, Hirsch FR, Kerr K, et al: Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: Guideline from the college of American pathologists, the international association for the study of lung cancer, and the association for molecular pathology. J Thorac Oncol. 13:323–358. 2018.PubMed/NCBI View Article : Google Scholar
6	Dandachi N, Tiran V, Lindenmann J, Brcic L, Fink-Neuboeck N, Kashofer K, Absenger G, Bezan A, Cote RJ, Datar R and Balic M: Frequency and clinical impact of preoperative circulating tumor cells in resectable non-metastatic lung adenocarcinomas. Lung Cancer. 113:152–157. 2017.PubMed/NCBI View Article : Google Scholar
7	Hofman V, Ilie MI, Long E, Selva E, Bonnetaud C, Molina T, Vénissac N, Mouroux J, Vielh P and Hofman P: Detection of circulating tumor cells as a prognostic factor in patients undergoing radical surgery for non-small-cell lung carcinoma: Comparison of the efficacy of the CellSearch Assay™ and the isolation by size of epithelial tumor cell method. Int J Cancer. 129:1651–1660. 2011.PubMed/NCBI View Article : Google Scholar
8	Hosokawa M, Kenmotsu H, Koh Y, Yoshino T, Yoshikawa T, Naito T, Takahashi T, Murakami H, Nakamura Y, Tsuya A, et al: Size-based isolation of circulating tumor cells in lung cancer patients using a microcavity array system. PLoS One. 8(e67466)2013.PubMed/NCBI View Article : Google Scholar
9	Negishi R, Hosokawa M, Nakamura S, Kanbara H, Kanetomo M, Kikuhara Y, Tanaka T, Matsunaga T and Yoshino T: Development of the automated circulating tumor cell recovery system with microcavity array. Biosens Bioelectron. 67:438–442. 2015.PubMed/NCBI View Article : Google Scholar
10	Hosokawa M, Yoshikawa T, Negishi R, Yoshino T, Koh Y, Kenmotsu H, Naito T, Takahashi T, Yamamoto N, Kikuhara Y, et al: Microcavity array system for size-based enrichment of circulating tumor cells from the blood of patients with small-cell lung cancer. Anal Chem. 85:5692–5698. 2013.PubMed/NCBI View Article : Google Scholar
11	Qian C, Wu S, Chen H, Zhang X, Jing R, Shen L, Wang X, Ju S, Jia C and Cong H: Clinical significance of circulating tumor cells from lung cancer patients using microfluidic chip. Clin Exp Med. 18:191–202. 2018.PubMed/NCBI View Article : Google Scholar
12	Bayarri-Lara C, Ortega FG, Cueto Ladrón de Guevara A, Puche JL, Ruiz Zafra J, de Miguel-Pérez D, Ramos AS, Giraldo-Ospina CF, Navajas Gómez JA, Delgado-Rodriguez M, et al: Circulating tumor cells identify early recurrence in patients with non-small cell lung cancer undergoing radical resection. PLoS One. 11(e0148659)2016.PubMed/NCBI View Article : Google Scholar
13	Okumura Y, Tanaka F, Yoneda K, Hashimoto M, Takuwa T, Kondo N and Hasegawa S: Circulating tumor cells in pulmonary venous blood of primary lung cancer patients. Ann Thorac Surg. 87:1669–1675. 2009.PubMed/NCBI View Article : Google Scholar
14	Nawa T, Nakagawa T, Mizoue T, Kusano S, Chonan T, Hayashihara K, Suito T and Endo K: A decrease in lung cancer mortality following the introduction of low-dose chest CT screening in Hitachi, Japan. Lung Cancer. 78:225–228. 2012.PubMed/NCBI View Article : Google Scholar
15	Maheswaran S, Sequist LV, Nagrath S, Ulkus L, Brannigan B, Collura CV, Inserra E, Diederichs S, Iafrate AJ, Bell DW, et al: Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med. 359:366–377. 2008.PubMed/NCBI View Article : Google Scholar