High expression of carcinoembryonic antigen and telomerase reverse transcriptase in circulating tumor cells is associated with poor clinical response to the immune checkpoint inhibitor nivolumab

Bao,Halin; Bai,Tuya; Takata,Koji; Yokobori,Takehiko; Ohnaga,Takashi; Hisada,Takeshi; Maeno,Toshitaka; Bao,Pinjie; Yoshida,Tomonori; Kumakura,Yuji; Honjo,Hiroaki; Sakai,Makoto; Sohda,Makoto; Fukuchi,Minoru; Altan,Bolag; Handa,Tadashi; Ide,Munenori; Miyazaki,Tatsuya; Ogata,Kyoichi; Oyama,Tetsunari; Shimizu,Kimihiro; Mogi,Akira; Asao,Takayuki; Shirabe,Ken; Kuwano,Hiroyuki; Kaira,Kyoichi

doi:10.3892/ol.2017.7671

March-2018 Volume 15 Issue 3

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March-2018 Volume 15 Issue 3

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Article Open Access

High expression of carcinoembryonic antigen and telomerase reverse transcriptase in circulating tumor cells is associated with poor clinical response to the immune checkpoint inhibitor nivolumab

Authors:
- Halin Bao
- Tuya Bai
- Koji Takata
- Takehiko Yokobori
- Takashi Ohnaga
- Takeshi Hisada
- Toshitaka Maeno
- Pinjie Bao
- Tomonori Yoshida
- Yuji Kumakura
- Hiroaki Honjo
- Makoto Sakai
- Makoto Sohda
- Minoru Fukuchi
- Bolag Altan
- Tadashi Handa
- Munenori Ide
- Tatsuya Miyazaki
- Kyoichi Ogata
- Tetsunari Oyama
- Kimihiro Shimizu
- Akira Mogi
- Takayuki Asao
- Ken Shirabe
- Hiroyuki Kuwano
- Kyoichi Kaira
View Affiliations / Copyright

Affiliations: Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma 371‑8511, Japan, Toyama Industrial Technology Center, Takaoka, Toyama 933‑0981, Japan, Department of Respiratory Medicine, Graduate School of Medicine, Gunma University, Maebashi, Gunma 371‑8511, Japan, Department of Oncology Clinical Development, Graduate School of Medicine, Gunma University, Maebashi, Gunma 371‑8511, Japan, Department of Diagnostic Pathology, Graduate School of Medicine, Gunma University, Maebashi, Gunma 371‑8511, Japan, Integrative Center of General Surgery, Gunma University Hospital, Maebashi, Gunma, 371-8510, Japan, Big Data Center for Integrative Analysis, Gunma University Initiative for Advance Research, Maebashi, Gunma 371‑8511, Japan

Copyright: © Bao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 3061-3067
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Published online on: December 20, 2017

https://doi.org/10.3892/ol.2017.7671
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Abstract

The present study aimed to enrich circulating tumor cells (CTCs) from blood samples using a new size‑sorting CTC chip. The present study also set out to identify a blood sensitivity marker for the immune checkpoint inhibitor nivolumab in patients with advanced, pre‑treatment lung cancer. The CTC sorting efficacy of the chip was investigated and the large cell fraction of blood samples from 15 patients with pre‑treatment lung cancer who were later administered nivolumab were purified. The expression levels of carcinoembryonic antigen (CEA), human Telomerase Reverse Transcriptase (hTERT), cytokeratin19 (CK19), and programmed death ligand‑1 (PD‑L1) were investigated to clarify the association between these CTC markers and the clinical response to nivolumab. The CTC chip effectively enriched cells from lung cancer cell line PC‑9. The large cell fraction had a high expression of CEA and hTERT, with the former being significantly associated with the clinical response to nivolumab. The expression of CEA and hTERT in CTCs derived from the blood of a patient with lung cancer were also validated. The evaluation of CEA and possibly hTERT in CTCs collected by the CTC chip may represent a promising predictive blood marker for sensitivity to nivolumab. To the best of our knowledge this is the first report to describe the predictive CTC marker for nivolumab in pre‑treatment patients.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

High expression of carcinoembryonic antigen and telomerase reverse transcriptase in circulating tumor cells is associated with poor clinical response to the immune checkpoint inhibitor nivolumab

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