A tissue microRNA signature that predicts the prognosis of breast cancer in young women

Ai Hironaka-Mitsuhashi, Juntaro Matsuzaki, Ryou U. Takahashi, Masayuki Yoshida, Yutaka Nezu, Yusuke Yamamoto, Sho Shiino, Takayuki Kinoshita, Toshikazu Ushijima, Nobuyoshi Hiraoka, Chikako Shimizu, Kenji Tamura, Takahiro Ochiya

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14 Citations (Scopus)

Abstract

Since breast cancers in young women are generally aggressive, young patients tend to be intensively treated with anti-cancer drugs. To optimize the strategy for treatment, particularly in young women, prognostic biomarkers are urgently required. The objective of this study was to identify a tissue microRNA (miRNA) signature that predicts prognosis in young breast cancer patients. Total RNA from 45 breast cancer patients aged <35 years was extracted from formalin-fixed paraffin-embedded (FFPE) tissues and analyzed using miRNA microarrays. Patients were categorized into two groups according to recurrence status within the 5 year period after surgery: recurrence (n = 11) and non-recurrent (n = 34). Histological parameters of hormone receptors and Ki-67 were statistically compared between the two groups. Differentially expressed miRNAs were identified, and their associations with overall survival (OS) were evaluated by log-rank test. The median observation period was 5.8 years for the recurrent group, and 9.1 years for the non-recurrent group. Nine miRNAs were significantly differentially expressed between the recurrent and non-recurrent groups. Receiver Operating Characteristic curve analysis was performed to evaluate the prediction accuracy of the identified miRNAs, and the resultant area under the curve was >0.7. Five of the miRNAs were validated by qRT-PCR, and the expression levels of three of those five (miR-183-5p, miR-194-5p, and miR-1285-5p), both alone and in combination, were associated with OS. In conclusion, we identified three candidate miRNAs that could be used separately or in combination as prognostic biomarkers in young breast cancer patients. This miRNA signature may enable selection of better treatment choices for young women with this disease.

Original languageEnglish
Article numbere0187638
JournalPloS one
Volume12
Issue number11
DOIs
Publication statusPublished - 2017 Nov

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Hironaka-Mitsuhashi, A., Matsuzaki, J., Takahashi, R. U., Yoshida, M., Nezu, Y., Yamamoto, Y., Shiino, S., Kinoshita, T., Ushijima, T., Hiraoka, N., Shimizu, C., Tamura, K., & Ochiya, T. (2017). A tissue microRNA signature that predicts the prognosis of breast cancer in young women. PloS one, 12(11), [e0187638]. https://doi.org/10.1371/journal.pone.0187638