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©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
Determination of esophageal squamous cell carcinoma and gastric adenocarcinoma on raw tissue using Raman spectroscopy
Hiroaki Ito, Naoyuki Uragami, Tomokazu Miyazaki, Yuto Shimamura, Haruo Ikeda, Yohei Nishikawa, Manabu Onimaru, Kai Matsuo, Masayuki Isozaki, William Yang, Kenji Issha, Satoshi Kimura, Machiko Kawamura, Noboru Yokoyama, Miki Kushima, Haruhiro Inoue
Hiroaki Ito, Naoyuki Uragami, Yuto Shimamura, Haruo Ikeda, Yohei Nishikawa, Manabu Onimaru, Kai Matsuo, Masayuki Isozaki, Noboru Yokoyama, Haruhiro Inoue, Digestive Disease Center, Showa University Koto Toyosu Hospital, Tokyo 135-8577, Japan
Tomokazu Miyazaki, JSR Corporation, Tokyo 105-0021, Japan
William Yang, Bay Spec Inc., San Jose, CA 95131, United States
Kenji Issha, Fuji Technical Research Inc., Yokohama 220-6215, Japan
Satoshi Kimura, Department of Laboratory Medicine and Central Clinical Laboratory, Showa University Northern Yokohama Hospital, Yokohama 224-8503, Japan
Machiko Kawamura, Department of Hematology, Saitama Cancer Center, Inamachi 362-0806, Japan
Miki Kushima, Department of Pathology, Showa University Koto Toyosu Hospital, Tokyo 135-8577, Japan
Author contributions: Ito H and Miyazaki T designed the study; Ito H was the guarantor, performed measurement, analysis, and interpretation of the data, and drafted the initial manuscript; Uragami N and Miyazaki T contributed to the acquisition, analysis, and interpretation of the data; Uragami N, Shimamura Y, Ikeda H, Nishikawa Y, Onimaru M, Matsuo K, and Isozaki M participated in the collection of the sample; Yang W designed and produced the Raman spectroscopy; Issha K continued importing the Raman spectroscopy; Kimura S, Kawamura M, Yokoyama N, Kushima M, and Inoue H revised the article critically for important intellectual content; Kushima M performed histopathological diagnosis of samples.
Supported by MEXT KAKENHI, JP17K09022 and JP20K07643.
Institutional review board statement: The study protocol was reviewed and approved (No. 18T5009) by the Institutional Review Board of Showa University Koto Toyosu Hospital.
Informed consent statement: All the participants provided written informed consent to participate in the study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
STROBE statement: The authors read the STROBE Statement checklist of items and the manuscript was prepared and revised according to the STROBE 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:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Hiroaki Ito, MD, PhD, Associate Professor, Digestive Disease Center, Showa University Koto Toyosu Hospital, 5-1-38 Toyosu, Koto-ku, Tokyo 135-8577, Japan. h.ito@med.showa-u.ac.jp
Received: December 12, 2022
Peer-review started: December 12, 2022
First decision: March 9, 2023
Revised: April 10, 2023
Accepted: April 27, 2023
Article in press: April 27, 2023
Published online: May 28, 2023
BACKGROUND
Cancer detection is a global research focus, and novel, rapid, and label-free techniques are being developed for routine clinical practice. This has led to the development of new tools and techniques from the bench side to routine clinical practice. In this study, we present a method that uses Raman spectroscopy (RS) to detect cancer in unstained formalin-fixed, resected specimens of the esophagus and stomach. Our method can record a clear Raman-scattered light spectrum in these specimens, confirming that the Raman-scattered light spectrum changes because of the histological differences in the mucosal tissue.
AIM
To evaluate the use of Raman-scattered light spectrum for detecting endoscop-ically resected specimens of esophageal squamous cell carcinoma (SCC) and gastric adenocarcinoma (AC).
METHODS
We created a Raman device that is suitable for observing living tissues, and attempted to acquire Raman-scattered light spectra in endoscopically resected specimens of six esophageal tissues and 12 gastric tissues. We evaluated formalin-fixed tissues using this technique and captured shifts at multiple locations based on feasibility, ranging from six to 19 locations 200 microns apart in the vertical and horizontal directions. Furthermore, a correlation between the obtained Raman scattered light spectra and histopathological diagnosis was performed.
RESULTS
We successfully obtained Raman scattered light spectra from all six esophageal and 12 gastric specimens. After data capture, the tissue specimens were sent for histopathological analysis for further processing because RS is a label-free methodology that does not cause tissue destruction or alterations. Based on data analysis of molecular-level substrates, we established cut-off values for the diagnosis of esophageal SCC and gastric AC. By analyzing specific Raman shifts, we developed an algorithm to identify the range of esophageal SCC and gastric AC with an accuracy close to that of histopathological diagnoses.
CONCLUSION
Our technique provides qualitative information for real-time morphological diagnosis. However, further in vivo evaluations require an excitation light source with low human toxicity and large amounts of data for validation.
Core Tip: Cancer diagnosis is a critical step in patient management, and involves a combination of diagnostic modalities or a single investigation. Diagnostic techniques that provide comprehensive data on the disease process can be particularly valuable, and Raman spectroscopy (RS) is one such modality that offers detailed molecular-level information. In this study, we utilized RS to rapidly detect cancer in resected esophageal and stomach specimens, providing information beyond morphology. By providing detailed molecular-level data, RS can provide a more comprehensive understanding of disease processes and aid in accurate diagnosis.
