miR-196b, miR-378a and miR-486 are predictive biomarkers for the efficacy of vaccine treatment in colorectal cancer

Shindo,Yoshitaro; Hazama,Shoichi; Nakamura,Yusuke; Inoue,Yuka; Kanekiyo,Shinsuke; Suzuki,Nobuaki; Takenouchi,Hiroko; Tsunedomi,Ryouichi; Nakajima,Masao; Ueno,Tomio; Takeda,Shigeru; Yoshino,Shigefumi; Okuno,Kiyotaka; Fujita,Yusuke; Hamamoto,Yoshihiko; Kawakami,Yutaka; Oka,Masaaki; Nagano,Hiroaki

doi:10.3892/ol.2017.6303

miR-196b, miR-378a and miR-486 are predictive biomarkers for the efficacy of vaccine treatment in colorectal cancer

Authors:
- Yoshitaro Shindo
- Shoichi Hazama
- Yusuke Nakamura
- Yuka Inoue
- Shinsuke Kanekiyo
- Nobuaki Suzuki
- Hiroko Takenouchi
- Ryouichi Tsunedomi
- Masao Nakajima
- Tomio Ueno
- Shigeru Takeda
- Shigefumi Yoshino
- Kiyotaka Okuno
- Yusuke Fujita
- Yoshihiko Hamamoto
- Yutaka Kawakami
- Masaaki Oka
- Hiroaki Nagano
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Affiliations: Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755‑8505, Japan, Department of Medicine and Surgery, The University of Chicago, Chicago, IL 60637, USA, Department of Surgery, Kinki University Faculty of Medicine, Osakasayama, Osaka 589‑8511, Japan, Department of Computer Science and Systems Engineering, Faculty of Engineering, Yamaguchi University, Ube, Yamaguchi 755‑8611, Japan, Division of Cellular Signaling, Institute for Advanced Medical Research; Keio University School of Medicine, Tokyo 160‑8582, Japan
Published online on: June 2, 2017 https://doi.org/10.3892/ol.2017.6303
Pages: 1355-1362
Copyright: © Shindo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

MicroRNAs (miRNAs/miRs) regulate the levels of transcripts and serve a critical function in the regulation of tumor microenvironments. Therefore, miRNA levels in cancer tissues are thought to be potential biomarkers for immunotherapy. From a phase I trial of a vaccine treatment using 5 human leukocyte antigen (HLA)‑A*2402‑restricted peptides (registration no. UMIN000004948), colorectal cancer (CRC) tissues were obtained from 8 patients and normal colorectal tissues from 5 patients via surgery. From a phase II trial using the same peptides (registration no. UMIN000001791), CRC tissues were obtained from 16 patients from the HLA‑A*2402‑matched group and 10 patients from the HLA‑A*2402‑unmatched group. These tissues were used for miRNA microarray analysis. As the first step, cancer tissues from the phase I study were used and 10 candidate miRNAs were selected by comparing the miRNA expression between two groups; one with improved prognosis and the other with poor prognosis. The miRNAs were subsequently validated using the cases enrolled in the phase II study. Significantly improved prognoses were identified in 16 patients in the HLA-A*2402‑matched group with high expression of miR‑196b‑5p and low expression of miR‑378a‑3p and miR‑486‑5p. There was no difference in prognosis in the 10 patients in the HLA‑A*2402‑unmatched group. Therefore, high miR‑196b expression and low miR‑378a‑3p and miR‑486‑5p expression were indicated as useful biomarkers for prediction of the efficacy of vaccine treatment for patients with metastatic CRC. In a planned phase III study, expression levels of these 3 miRNAs (miR‑196b‑5p, miR‑378a‑3p and miR‑486‑5p) may be useful biomarkers for assessing patients who are likely to have an improved outcome following vaccination.

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