Research Papers:

Differential expression of exosomal miRNAs between breast cancer patients with and without recurrence

Aiko Sueta, Yutaka Yamamoto _, Mai Tomiguchi, Takashi Takeshita, Mutsuko Yamamoto-Ibusuki and Hirotaka Iwase

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Oncotarget. 2017; 8:69934-69944. https://doi.org/10.18632/oncotarget.19482

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Aiko Sueta1, Yutaka Yamamoto1, Mai Tomiguchi1, Takashi Takeshita1, Mutsuko Yamamoto-Ibusuki2 and Hirotaka Iwase1

1Department of Breast and Endocrine Surgery, Kumamoto University Graduate School of Medical Sciences, Kumamoto 860-8556, Japan

2Department of Molecular-Targeting Therapy for Breast Cancer, Kumamoto University Hospital, Kumamoto 860-8556, Japan

Correspondence to:

Yutaka Yamamoto, email: [email protected]

Keywords: exosome, microRNA, breast cancer, circulating biomarker, prognostic factor

Received: April 19, 2017    Accepted: June 28, 2017    Published: July 22, 2017


Background: Exosomal microRNAs (miRNAs) are promising candidate biomarkers for diagnosis or prognosis for breast cancer. We investigated the prognostic role of exosomal miRNAs in serum samples derived from patients with breast cancer and compared miRNA expression between serum and tumor tissues.

Methods: The miRNA profile derived from exosome between breast cancer patients with recurrence (n = 16) and without recurrence (n = 16) were compared by miRNA PCR array. Further, we examined the expression of miRNAs derived from tissues in the patients with breast cancer with (n = 35) and without recurrence (n = 39) by qRT-PCR.

Results: Of 384 miRNAs, three miRNAs (miR-338-3p, miR-340-5p, and miR-124-3p) were significantly upregulated and eight (miR-29b-3p, miR-20b-5p, miR-17-5p, miR-130a-3p, miR-18a-5p, miR-195-5p, miR-486-5p, and miR-93-5p) were significantly downregulated in the patients with recurrence. We evaluated the expression of the miRNAs in tumor tissues. The patients with recurrence had higher levels of miR-340 at their primary site as well as in the serum. In contrast, miR-195-5p, miR-17-5p, miR-93-5p, and miR-130a-3p, derived from tumor tissues that were downregulated in the serum from patients with recurrence, were higher in the patients with recurrence than in those with no recurrence. In logistic regression analysis, miR-340-5p, miR-17-5p, miR-130a-3p, and miR-93-5p were significantly associated with recurrence.

Conclusions: Several exosomal miRNAs may be useful biomarkers to predict breast cancer recurrence. We show the different expression patterns of miRNAs between tumor tissues and serum. These findings may suggest selective mechanism of release of exosomal miRNAs by cancer cells to regulate their progression.

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