Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Oct 15, 2018; 10(10): 344-350
Published online Oct 15, 2018. doi: 10.4251/wjgo.v10.i10.344
miR-122-5p as a novel biomarker for alpha-fetoprotein-producing gastric cancer
Suguru Maruyama, Shinji Furuya, Kensuke Shiraishi, Hiroki Shimizu, Hidenori Akaike, Naohiro Hosomura, Yoshihiko Kawaguchi, Hidetake Amemiya, Hiromichi Kawaida, Makoto Sudo, Shingo Inoue, Hiroshi Kono, Daisuke Ichikawa
Suguru Maruyama, Shinji Furuya, Kensuke Shiraishi, Hiroki Shimizu, Hidenori Akaike, Naohiro Hosomura, Yoshihiko Kawaguchi, Hidetake Amemiya, Hiromichi Kawaida, Makoto Sudo, Shingo Inoue, Hiroshi Kono, Daisuke Ichikawa, First Department of Surgery, Faculty of Medicine University of Yamanashi, Yamanashi 409-3898, Japan
Author contributions: Maruyama S performed the majority of experiments and wrote the manuscript; Furuya S performed the research; Shiraishi K, Akaike H and Kawaguchi Y provided tissue samples and clinical data; Shimizu H, Hosomura N, Amemiya H, Kawaida H, Sudo M, Inoue S and Kono H made substantial contributions to the data analysis and interpretation; Ichikawa D designed the research and helped to draft the manuscript.
Institutional review board statement: This study was approved by the Ethics Committee of Yamanashi University (approved number: 1825) and was performed in accordance with the ethical standards of the Declaration of Helsinki and its later amendments.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
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: Daisuke Ichikawa, MD, PhD, Professor, First Department of Surgery, Faculty of Medicine University of Yamanashi, 1110 Shimokato, Chuou, Yamanashi 409-3898, Japan. dichikawa@yamanashi.ac.jp
Telephone: +81-55-2737390 Fax: +81-55-2737390
Received: July 4, 2018
Peer-review started: July 5, 2018
First decision: July 24, 2018
Revised: August 5, 2018
Accepted: August 30, 2018
Article in press: August 31, 2018
Published online: October 15, 2018
Abstract
AIM

To investigate the clinical utility of alpha-fetoprotein (AFP)-producing gastric cancer (AFPGC)-specific microRNA (miRNA) for monitoring and prognostic prediction of patients.

METHODS

We performed a comprehensive miRNA array-based approach to compare miRNA expression levels between AFP-positive and AFP-negative cells in three patients with primary AFPGC. We next examined the expression levels of the selected miRNAs in five AFPGC and ten non-AFPGC tissue samples by quantitative reverse transcription-polymerase chain reaction to validate their utility. We also investigated the expression levels of the selected miRNA not only in tissue but also in plasma samples. Moreover, we investigated the relationship between plasma AFP levels and plasma selected miRNA expression levels, and also investigated the correlation of the selected miRNA expression levels and malignant potential.

RESULTS

Among the five miRNAs selected from the miRNA array results, the expression levels of miR-122-5p were significantly higher in the AFPGC patients than in the non-AFPGC patients (P < 0.05). In tissue samples, miR-122-5p expression level tended to be lower in the non-AFPGC tissue than the normal gastric mucosa. Conversely, in the AFPGC tissue, miR-122-5p expression level was significantly higher in the AFPGC tissue than both the normal gastric mucosa and the non-AFPGC tissue samples (P < 0.05). Plasma miR-122-5p expression levels were also significantly higher in the AFPGC patients than the health volunteers and the non-AFPGC patients (P < 0.05) and were strongly correlated with plasma AFP levels (r = 0.7975, P < 0.0001). Moreover, the correlation of miR-122-5p expression in tissue samples with malignant potential was stronger than that of plasma AFP level in the AFPGC patients. In contrast, no correlation was found between miR-122-5p expression levels and liver metastasis in the non-AFPGC patients.

CONCLUSION

miR-122-5p might be a useful biomarker for early detection and disease monitoring in AFPGC.

Keywords: Gastric cancer, Alpha-fetoprotein, Alpha-fetoprotein producing gastric cancer, MicroRNA, miR-122-5p

Core tip: We examined the microRNAs (miRNA) expression in alpha-fetoprotein (AFP)-producing gastric cancer (AFPGC) tissue samples using a comprehensive miRNA array-based approach, and also investigated the clinical utility of the identified AFPGC-specific miRNAs. We found the expression of miR-122-5p was significantly higher in the AFPGC tissues and plasma samples. Moreover, tissue miR-122-5p expression levels exhibited a stronger correlation with malignant potential than plasma AFP level in AFPGC patients. miR-122-5p might be a useful biomarker for early detection and disease monitoring in AFPGC.