Retrospective Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 28, 2020; 26(4): 424-432
Published online Jan 28, 2020. doi: 10.3748/wjg.v26.i4.424
Cancer/testis antigen, Kita-Kyushu lung cancer antigen-1 and ABCD stratification for diagnosing gastric cancers
Akiko Shida, Takashi Fukuyama, Nobue Futawatari, Haruki Ohmiya, Yoshinobu Ichiki, Tetsuro Yamashita, Yatsushi Nishi, Noritada Kobayashi, Hitoshi Yamazaki, Masahiko Watanabe, Yoshihito Takahashi
Akiko Shida, Division of Pathology, Kitasato University, Sagamihara, Kanagawa 252-0374, Japan
Takashi Fukuyama, Noritada Kobayashi, Division of Biomedical Research, Kitasato University Medical Center, Kitamoto, Saitama 364-8501, Japan
Nobue Futawatari, Division of Surgery, Toho University, Ohashi Medical Center, Meguroku, Tokyo 153-8515, Japan
Haruki Ohmiya, Tetsuro Yamashita, Department of Biological Chemistry and Food Sciences, Faculty of Agriculture, Iwate University, Morioka, Iwate 020-8505, Japan
Yoshinobu Ichiki, Department of General Thoracic Surgery, National Hospital Organization Saitama Hospital, Wako, Saitama 364-8501, Japan
Yatsushi Nishi, Yoshihito Takahashi, Division of Surgery, Kitasato University Medical Center, Kitamoto, Saitama 364-8501, Japan
Hitoshi Yamazaki, Division of Pathology, Kitasato University Medical Center, Kitamoto, Saitama 364-8501, Japan
Masahiko Watanabe, Division of Surgery, Kitasato University, Sagamihara, Kanagawa 252-0374, Japan
Author contributions: Shida A and Fukuyama T designed the research; Shida A, Fukuyama T, Futawatari N, Yamazaki H, Ichiki Y, Takahashi Y, Nishi Y, Kobayashi N and Watanabe M performed the research; Fukuyama T, Haruki Ohmiya and Tetsuro Yamashita performed statistical analysis; Shida A and Fukuyama T wrote the paper.
Supported by Grant-in-Aid for research by the Kitasato University Medical Center, No. H26-008; the JSPS KAKENHI, No. 17K16578; Takeda Science Foundation; Kitasato University Research Grant for Young Researchers; Grant-in-Aid for research from the Kitasato University Medical Center, No. H25-0006; and the JSPS KAKENHI, No. 26670609.
Institutional review board statement: The study protocol was approved by the Human Ethics Review Committee of Kitasato University Medical Center, Japan
Informed consent statement: All study patients were not to give informed consent to the study because the analysis used anonymous clinical date that were obtained after each patient agreed to use surgical specimen for researches by written consent.
Conflict-of-interest statement: There are no conflicts of interest to declare.
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: Takashi Fukuyama, PhD, Investigator, Division of Biomedical research, Kitasato University Medical Center, 6-100 Arai, Kitamoto, Saitama 364-8501, Japan. fukuyam@insti.kitasato-u.ac.jp
Received: November 23, 2019
Peer-review started: November 23, 2019
First decision: December 12,2019
Revised: December 23, 2019
Accepted: January 11, 2020
Article in press: January 11, 2020
Published online: January 28, 2020
ARTICLE HIGHLIGHTS
Research background

Gastric cancer (GC) is still leading cause of cancer-related deaths, so that we need to diagnose in early stage and to investigate novel therapy for advanced stage like immunotherapy. Recently, ABCD classification, noninvasive population screening process combining the assay of anti-Helicobacter pylori (H. pylori) antibody and serum pepsinogen (PGI, PGII, refrecting status of atrophic gastric mucosa), is adapted to recognize high-risk patients in some parts of Japan.

Research motivation

KK-LC-1, a cancer/testis antigen, is frequently expressing in early stage of GC same as advanced stage. KK-LC-1 may be useful target for diagnosis of GC in early stage and may be adapted for immunotherapy in advanced stage.

Research objectives

We evaluated the effectiveness of KK-LC-1 and ABCD stratification in the diagnosis of GC by examination of KK-LC-1 expression and ABCD stratification on patients with GC.

Research methods

We analyzed the gene expression of KK-LC-1 in surgical specimens obtained from GC tumors. The levels of serum PGI/PGII and IgG against H. pylori were measured. According to their serological status, the patients were classified into the four groups of the ABCD stratification.

Research results

Of the 77 examined patients, 63(81.8%) expressed KK-LC-1. The IgG titers of H. pylori and PGIIwere significantly higher in patients expressing KK-LC-1 than those measured in patients not expressing KK-LC-1 (P = 0.0289 and P = 0.0041, respectively). The expression of KK-LC-1 in Group C[PG method (+)/H. pylori infection (+)] was as high as 93.9% high.

Research conclusions

The expression of KK-LC-1 in GC was associated with H. pylori infection and atrophic status. The frequency of KK-LC-1 expression in GC was high, especially in Group C. Therefore, KK-LC-1 may be a useful marker for the diagnosis of GC. Moreover, the ABCD stratification is useful for the detection of KK-LC-1 expression in patients with GC.

Research perspectives

Noninvasive detection system for KK-LC-1, such as using liquid biopsies would be expected for following high-risk group after ABCD stratification or endoscopic examination.