Terasawa H, Kinugasa H, Nouso K, Yamamoto S, Hirai M, Tanaka T, Takaki A, Okada H. Circulating tumor DNA dynamics analysis in a xenograft mouse model with esophageal squamous cell carcinoma. World J Gastroenterol 2021; 27(41): 7134-7143 [PMID: 34887633 DOI: 10.3748/wjg.v27.i41.7134]
Corresponding Author of This Article
Hideaki Kinugasa, MD, PhD, Doctor, Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-Cho Kita-Ku, Okayama 7008558, Japan. gyacy14@gmail.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Hiroyuki Terasawa, Hideaki Kinugasa, Kazuhiro Nouso, Shumpei Yamamoto, Mami Hirai, Akinobu Takaki, Hiroyuki Okada, Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 7008558, Japan
Takehiro Tanaka, Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 7008558, Japan
Author contributions: Kinugasa H designed the manuscript; Terasawa H drafted the manuscript; Kinugasa H, Terasawa H, Yamamoto S, Hirai M, Tanaka T and Takaki A were responsible for experiments; Kinugasa H, Nouso K and Okada H supervised the manuscript preparation; all authors approved the final manuscript.
Supported byJSPS KAKENHI (19k17433).
Institutional review board statement: This study was reviewed approved by [the ethics committee of Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital] Institutional Review Board.
Institutional animal care and use committee statement: Xenograft mouse experimental protocols were approved by the Ethical Committee of Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences (OKU-2019276).
Conflict-of-interest statement: The authors declare that there are no conflicts of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hideaki Kinugasa, MD, PhD, Doctor, Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-Cho Kita-Ku, Okayama 7008558, Japan. gyacy14@gmail.com
Received: May 14, 2021 Peer-review started: May 14, 2021 First decision: July 14, 2021 Revised: July 21, 2021 Accepted: August 30, 2021 Article in press: August 30, 2021 Published online: November 7, 2021 Processing time: 175 Days and 20.5 Hours
ARTICLE HIGHLIGHTS
Research background
The clinical application of liquid biopsy is becoming more widespread. However, it remains unclear which factors, such as tumor volume and tumor invasion, influence circulating tumor DNA (ctDNA), and the origin of ctDNA in liquid biopsy is always problematic.
Research motivation
It will be very important to address the origin and dynamics of ctDNA for further clinical application of liquid biopsy.
Research objectives
A xenograft mouse model was used to assess the origin of ctDNA, clarify the dynamics of ctDNA levels, assess ctDNA levels after treatment, and determine whether tumor volume and invasion are related to ctDNA levels.
Research methods
Tumor xenotransplants were established by inoculating BALB/c-nu/nu mice with the TE11 cell line (esophageal squamous cell carcinoma). Analysis of ctDNA was performed by droplet digital polymerase chain reaction, using the human telomerase reverse transcriptase (hTERT) gene.
Research results
Mice given two-site xenografts were sacrificed for ctDNA at week 4 and week 8. No hTERT was detected at week 4, but it was detected at week 8. However, in four-site xenograft mice, hTERT was detected both at week 4 and week 6. These experiments revealed that both tumor invasion and tumor volume were associated with the detection of ctDNA. In resection experiments, hTERT was detected at resection, but had decreased by 6 h, and was no longer detected 1 and 3 d after resection. The half-life of ctDNA was estimated to be 1.8-3.2 h.
Research conclusions
We clarified the origin and dynamics of ctDNA, showing that not only tumor invasion but also tumor volume was an important factor. Also, ctDNA could be measured at 1 d after tumor resection to evaluate the residuals.
Research perspectives
In the clinical application of liquid biopsy, early-stage cancers could be targeted, and post-treatment monitoring should be performed 1 d after treatment.
