MicroRNA analysis of breast ductal fluid in breast cancer patients

Abstract

Recent studies suggest that microRNAs show promise as excellent biomarkers for breast cancer; however there is still a high degree of variability between studies making the findings difficult to interpret. In addition to blood, ductal lavage (DL) and nipple aspirate fluids represent an excellent opportunity for biomarker detection because they can be obtained in a less invasive manner than biopsies and circumvent the limitations of evaluating blood biomarkers with regards to tissue of origin specificity. In this study, we have investigated for the first time, through a real-time PCR array, the expression of 742 miRNAs in the ductal lavage fluid collected from 22 women with unilateral breast tumors. We identified 17 differentially expressed miRNAs between tumor and paired normal samples from patients with ductal breast carcinoma. Most of these miRNAs have various roles in breast cancer tumorigenesis, invasion and metastasis, therapeutic response, or are associated with several clinical and pathological characteristics of breast tumors. Moreover, some miRNAs were also detected in other biological fluids of breast cancer patients such as serum (miR-23b, -133b, -181a, 338-3p, -625), plasma (miR-200a), and breast milk (miR-181a). A systems biology analysis of these differentially expressed miRNAs points out possible pathways and cellular processes previously described as having an important role in breast cancer such as Wnt, ErbB, MAPK, TGF-β, mTOR, PI3K-Akt, p53 signaling pathways. We also observed a difference in the miRNA expression with respect to the histological type of the tumors. In conclusion, our findings suggest that miRNA analysis of breast ductal fluid is feasible and potentially very useful for the detection of breast cancer.

Milk MicroRNAs in Health and Disease

“…The first study focusing on milk microRNAs was only reported in 2010 (Hata et al., ; Kosaka et al., ) and opened a very new field of research focused on milk microRNAs. From then on, a number of studies have focused on investigating milk microRNAs profiles in various conditions including mammary gland infections (Sun et al., ), breast cancer (Do Canto et al., ; Gu et al., ; Pigati et al., ), lactation periods (Hou et al., ; Na et al., ; Xi et al., ), milk processing (Howard et al., ; Oh et al., ), and digestion (Benmoussa et al., ; Kahn et al., ; Liao, Du, Li, & Lonnerdal, ).…”

“…In milk, microRNA expression was related to mammary gland conditions, including infections (Iannaccone et al., ; Lai et al., , ; Sun et al., ), cancer (Decmann et al., ; Do Canto et al., ; Hesari et al., ), pregnancy and lactation status (Carney et al., ; Perri et al., ; Schanzenbach et al., ), and maternal diet (Chen et al., ). Therefore microRNAs in milk were studied for their potential as biomarkers (Gustafson, Tyryshkin, & Renwick, ; Melnik & Schmitz, ) such as quality controls of commercial milk (Oh et al., ).…”

“…Research on human breast milk showed that the immense majority of milk microRNA are immunity‐modulating microRNAs (Benmoussa et al., , ; Chen et al., ; Cui et al., ; Golan‐Gerstl et al., ; Hata et al., ; Izumi et al., ; Kosaka et al., ; Melnik, John, & Schmitz, ; Munch et al., ; Na et al., ; Zempleni et al., , ; Zhou et al., ), with some of these differentially expressed during breast cancer development in vitro (Pigati et al., ) and in vivo (Do Canto et al., ). Nevertheless, the data on cancer and breast milk microRNAs remain scarce and need further compilations.…”

Metabolomic profiling of breast tumors using ductal fluid

“…They showed that NAF is metabolically distinct from matched plasma samples which supports the theory that the cellular environment (tumor microenvironment) is more directly mirrored in breast biofluids (DL and NAF). We have recently identified a panel of microRNAs that are differentially expressed in ductal fluid from breasts with tumors compared to paired ductal fluid samples from the contralateral normal breast (19), further substantiating the importance of a more direct analysis of the tumor microenvironment and the potential for biomarker development using ductal fluid obtained in a non-invasive or minimally invasive approach. Here, we report the first metabolomic analysis of breast ductal fluid samples obtained from 43 patients with unilateral breast cancer.…”

Tissue microRNAs as Cancer Tissue Biomarkers

“…However, serum and plasma can also be monitored as significant differences were found in miRNA levels between breast cancer patients and controls. Only as recently as 2016 has DL fluid been studied for potential use in miRNA detection for cancers [19].…”