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©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
Early gastric cancer frequently has high expression of KK-LC-1, a cancer-testis antigen
Nobue Futawatari, Takashi Fukuyama, Rui Yamamura, Akiko Shida, Yoshihito Takahashi, Yatsushi Nishi, Yoshinobu Ichiki, Noritada Kobayashi, Hitoshi Yamazaki, Masahiko Watanabe
Nobue Futawatari, Department of Surgery, Sagamihara National Hospital, Sagamihara, Kanagawa 252-0392, Japan
Nobue Futawatari, Akiko Shida, Masahiko Watanabe, Department of Surgery, School of Medicine, Kitasato University, Sagamihara, Kanagawa 252-0374, Japan
Takashi Fukuyama, Rui Yamamura, Noritada Kobayashi, Division of Biomedical Research, Kitasato University Medical Center, Kitamoto, Saitama 364-8501, Japan
Yoshihito Takahashi, Yatsushi Nishi, Department of Surgery, Kitasato University Medical Center, Kitamoto, Saitama 364-8501, Japan
Yoshinobu Ichiki, Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka 807-8555, Japan
Hitoshi Yamazaki, Department of Pathology, Kitasato University Medical Center, Kitamoto, Saitama 364-8501, Japan
Author contributions: Futawatari N and Fukuyama T contributed equally to this work; Futawatari N, Fukuyama T, Ichiki Y, Yamazaki H and Watanabe M designed the research; Futawatari N, Fukuyama T, Yamamura R, Shida A, Takahashi Y, Nishi Y, Kobayashi N and Yamazaki H performed the research; Futawatari N performed statistical analysis; Futawatari N, Fukuyama T and Watanabe M wrote the paper.
Supported by Grant-in-Aid for research by Kitasato University Medical Center, No. H25-0006 and the JSPS, KAKENHI, No. 26670609 to Futawatari N, and the JSPS, KAKENHI, No. 21700510 and No. 17K16578, Takeda Science Foundation and Kitasato University Research Grant for Young Researchers to Fukuyama T.
Institutional review board statement: The study protocol was approved by the Human Ethics Review Committee of Kitasato University Medical Center, Japan.
Conflict-of-interest statement: There are no conflicts of interest to declare.
Data sharing statement: No additional data are available.
Open-Access: 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/
Correspondence to: Takashi Fukuyama, PhD, Investigator, Division of Biomedical Research, 6-100 Arai, Kitamoto, Saitama 364-8501, Japan.
fukuyam@insti.kitasato-u.ac.jp
Telephone: +81-48-5931236 Fax: +81-48-5931262
Received: October 5, 2017
Peer-review started: October 6, 2017
First decision: October 18, 2017
Revised: October 30, 2017
Accepted: November 14, 2017
Article in press: November 14, 2017
Published online: December 14, 2017
Processing time: 68 Days and 1.3 Hours
AIM
To assess cancer-testis antigens (CTAs) expression in gastric cancer patients and examined their associations with clinicopathological factors.
METHODS
Eighty-three gastric cancer patients were evaluated in this study. Gastric cancer specimens were evaluated for the gene expression of CTAs, Kitakyushu lung cancer antigen-1 (KK-LC-1), melanoma antigen (MAGE)-A1, MAGE-A3 and New York esophageal cancer-1 (NY-ESO-1), by reverse transcription PCR. Clinicopathological background information, such as gender, age, tumor size, macroscopic type, tumor histology, depth of invasion, lymph node metastasis, lymphatic invasion, venous invasion, and pathological stage, was obtained. Statistical comparisons between the expression of each CTA and each clinicopathological background were performed using the χ2 test.
RESULTS
The expression rates of KK-LC-1, MAGE-A1, MAGE-A3, and NY-ESO-1 were 79.5%, 32.5%, 39.8%, and 15.7%, respectively. In early stage gastric cancer specimens, the expression of KK-LC-1 was 79.4%, which is comparable to the 79.6% observed in advanced stage specimens. The expression of KK-LC-1 was not significantly associated with clinicopathological factors, while there were considerable differences in the expression rates of MAGE-A1 and MAGE-A3 with vs without lymphatic invasion (MAGE-A1, 39.3% vs 13.6%, P = 0.034; MAGE-A3, 47.5% vs 18.2%, P = 0.022) and/or vascular invasion (MAGE-A1, 41.5% vs 16.7%, P = 0.028; MAGE-A3, 49.1% vs 23.3%, P = 0.035) and, particularly, MAGE-A3, in patients with early vs advanced stage (36.5% vs 49.0%, P = 0.044), respectively. Patients expressing MAGE-A3 and NY-ESO-1 were older than those not expressing MAGE-A3 and NY-ESO-1 (MAGE-A3, 73.7 ± 7.1 vs 67.4 ± 12.3, P = 0.009; NY-ESO-1, 75.5 ± 7.2 vs 68.8 ± 11.2, P = 0.042).
CONCLUSION
The KK-LC-1 expression rate was high even in patients with stage I cancer, suggesting that KK-LC-1 is a useful biomarker for early diagnosis of gastric cancer.
Core tip: The Kitakyushu lung cancer antigen-1 (KK-LC-1) is a relatively later cancer-testis antigen and has received interest because it was reported that KK-LC-1 is a predominant antigen for cancer immunotherapy. We found that the expression rate of KK-LC-1 in gastric cancer was 79.5%, which was higher than that of other cancer-testis antigens and the same as that in both early- and late-stage patients. KK-LC-1 is a potential biomarker for early detection of gastric cancer and identification of patients at high risk for gastric cancer. Furthermore, KK-LC-1 is a potential target for immunotherapy in gastric cancer.
