In recent years, there has been a concerted effort to identify biomarkers derived from body fluid in various cancers. Exosomal microRNA (miRNA) has been used as one of useful diagnostic or prognostic biomarkers. We aimed to investigate the prognostic role of the exosomal miRNAs in serum samples derived from patients with primary breast cancer. Additionally, we evaluated whether the exosomal miRNA in serum reflect the origin of primary tumor by means of comparing their expression levels between in serum and tumors.
Patients and Methods
Exosomes in serum sample (500uL) were extracted using ExoQuick (System Biosciences) and miRNAs were isolated using SeraMirTM Exosome RNA Amplification Kit (SBI). We compared the miRNA profile derived from exosome between the patients with breast cancer with recurrence (n=16) and without recurrence (n=16) by miRNA PCR array. Further, we examined the expression of miRNA derived from tumor tissues in the patients with breast cancer recurrence (n=35) and without recurrence (n=39) by qRT-PCR. All samples were collected before treatment and surgery.
Of the 384 miRNAs, 11 miRNAs were significantly expressed; three miRNAs (miR-338-3p, miR-340-5p, and miR-124-3p) were significantly up-regulated 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-93a-5p) were significantly down-regulated in the patients with recurrence compared to those without recurrence. Next, we evaluated expression of the above miRNAs in tumor tissues. The patients with recurrence have higher levels of miR-340 at their primary site as well as in the serum. On the contrary, miR-195-5p, miR-17-5p, miR-93-5p, and miR-130a-3p derived from tumor tissues that were down-regulated in the patients with recurrence in serum, were highly expressed in the patients with recurrence than those with no-recurrence. In logistic regression analysis, tumor size, miR-340-5p, miR-17-5p, miR-130a-3p, and miR-93-5p were significantly associated with breast cancer recurrence (each P < 0.05).
Several exosomal miRNAs at diagnosis may be useful biomarker to predict the breast cancer recurrence. Moreover, we showed the different expression pattern of miRNAs between tumor tissues and serum. These findings may suggest selective mechanism of release of exosomal miRNA by cancer cells to regulate their progression. Further studies to confirm our results are needed.
Citation Format: Sueta A, Yamamoto Y, Tomiguchi M, Takeshita T, Ibusuki M, Iwase H. Differential expression of exosomal miRNAs between breast cancer patients with recurrence and no-recurrence [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-02-13.