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

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

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1355-1362
Number of pages8
JournalOncology Letters
Volume14
Issue number2
DOIs
Publication statusPublished - 2017

Keywords

  • Colorectal cancer
  • Efficacy
  • MicroRNA
  • Peptide vaccine
  • Predictive biomarker

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Shindo, Y., Hazama, S., Nakamura, Y., Inoue, Y., Kanekiyo, S., Suzuki, N., Takenouchi, H., Tsunedomi, R., Nakajima, M., Ueno, T., Takeda, S., Yoshino, S., Okuno, K., Fujita, Y., Hamamoto, Y., Kawakami, Y., Oka, M., & Nagano, H. (2017). miR-196b, miR-378a and miR-486 are predictive biomarkers for the efficacy of vaccine treatment in colorectal cancer. Oncology Letters, 14(2), 1355-1362. https://doi.org/10.3892/ol.2017.6303