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©The Author(s) 2026. Published by Baishideng Publishing Group Inc. All rights reserved.
Kita-Kyushu lung cancer antigen-1 expression in initial gastric tumors predicts multiple cancer development: A pilot study
Nobue Futawatari, Takashi Fukuyama, Yusuke Akimoto, Junji Maehara, Daisuke Hihara, Yosuke Okamoto, Yuki Yokouchi, Kei Takahashi, Manabu Watanabe, Yoshihisa Saida
Nobue Futawatari, Department of Surgery, National Hospital Organization Sagamihara National Hospital, Sagamihara 252-0395, Kanagawa, Japan
Nobue Futawatari, Yusuke Akimoto, Junji Maehara, Manabu Watanabe, Yoshihisa Saida, Department of Surgery, Toho University Ohashi Medical Center, Ohashi Meguro-Ku 153-8515, Tokyo, Japan
Takashi Fukuyama, Division of Biomedical Research, Kitasato University Medical Center, Kitamoto 364-8501, Saitama, Japan
Daisuke Hihara, Yosuke Okamoto, Department of Gastroenterology, Toho University Ohashi Medical Center, Ohashi Meguro-Ku 153-8515, Tokyo, Japan
Yuki Yokouchi, Kei Takahashi, Department of Pathology, Toho University Ohashi Medical Center, Ohashi Meguro-Ku 153-8515, Tokyo, Japan
Author contributions: Futawatari N participated in study design, data collection and analysis; Futawatari N and Fukuyama T drafted the manuscript; Akimoto Y, Maehara J, and Hihara D, and Okamoto Y performed data collection; Yokouchi Y and Takahashi K advised on pathology; Takahashi K, Watanabe M, and Saida Y revised the manuscript. All authors read and approved the final manuscript.
Institutional review board statement: The Human Ethics Review Committee of Toho University Ohashi Medical Center, Japan (Approval No.H23034_H20023) approved the study protocol. All the experiments were performed in accordance with relevant guidelines and regulations.
Informed consent statement: All patients signed an informed consent prior to resection of the tissue samples used in this study.
Conflict-of-interest statement: A patent application is being prepared related to the use of the target expression as a biomarker for predicting multiple gastric cancer development. The authors declare that they have no conflict of interest.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: Data is provided within the manuscript or supplementary information files. Deidentified data supporting this study’s findings are available from the corresponding author upon reasonable request.
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: Takashi Fukuyama, PhD, Division of Biomedical Research, Kitasato University Medical Center, Arai 6-100, Kitamoto 364-8501, Saitama, Japan.
fukuyam@insti.kitasato-u.ac.jp
Received: August 31, 2025
Revised: October 16, 2025
Accepted: December 10, 2025
Published online: January 24, 2026
Processing time: 144 Days and 4.5 Hours
BACKGROUND
We have previously reported that the cancer/testis antigen Kita-Kyushu lung cancer antigen-1 (KK-LC-1) is frequently expressed in gastric cancer (GC), with a particularly high positivity rate observed in patients with multiple GCs. Thus, we conducted a preliminary study to further investigate the relationship between KK-LC-1 expression and multiple GCs. Specifically, we aimed to explore the potential clinical utility of KK-LC-1 as a biomarker for identifying patients at risk of developing multiple gastric cancers, with a focus on its expression in the initial tumor lesions.
AIM
To investigate the association between KK-LC-1 expression and the development of multiple GCs in a preliminary cohort.
METHODS
Among 124 patients (177 lesions) treated for GC at Toho University Medical Center Ohashi Hospital between September 2020 and November 2023, 109 (single cancer: 82; multiple cancers: 27) with available initial tumor specimens were enrolled. KK-LC-1 expression was assessed using immunohistochemistry, and clinicopathological correlations were analyzed using Fisher’s exact test. Tumor locations were classified anatomically and analyses were performed, focusing on the initial cancer sites.
RESULTS
In tumors located in the upper stomach, KK-LC-1 expression did not correlate with clinicopathological features. However, in the middle and lower stomach, KK-LC-1 expression was significantly associated with older age, differentiated histological types, and multiple cancers. Notably, all patients with multiple GCs had KK-LC-1-positive tumors (100%) in their initial lesions. The KK-LC-1 positivity rate in the initial tumors of multiple cancers in the middle and lower region was significantly higher than that in solitary cancers. Conversely, the absence of KK-LC-1 expression in a solitary tumor located in the middle and lower region may suggest a reduced risk for the subsequent development of multiple primary cancers.
CONCLUSION
KK-LC-1 expression in the initial gastric tumors, particularly in the middle and lower stomach regions, may serve as a predictive biomarker for the future development of multiple GCs.
Core Tip: We have previously reported that the cancer/testis antigen Kita-Kyushu lung cancer antigen-1 (KK-LC-1) is frequently expressed in gastric cancer (GC), with high expression observed in multiple GCs. Therefore, as a preliminary study, we investigated the relationship between KK-LC-1 expression and multiple GCs, focusing on its potential clinical utility. In the middle and lower stomach regions, KK-LC-1 expression was significantly associated with older age, differentiated histological type, and the presence of multiple cancers, with all cases in the multiple cancer group exhibiting KK-LC-1 positivity (100%). KK-LC-1 expression in primary gastric tumors suggests a higher risk of subsequent development of multiple GCs.
