title: 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.
authors.affiliation: Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University Medical Center, Georgetown University, Washington, DC, USA.
authors.forename: Luisa Matos
authors.initials: LM
authors.lastname: Do Canto
authors.affiliation: Biochemistry Department, 'Victor Babes' University of Medicine and Pharmacy, Timisoara, Romania.
authors.forename: Catalin
authors.initials: C
authors.lastname: Marian
authors.affiliation: Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University Medical Center, Georgetown University, Washington, DC, USA.
authors.forename: Shawna
authors.initials: S
authors.lastname: Willey
authors.affiliation: Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University Medical Center, Georgetown University, Washington, DC, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Sidawy
authors.affiliation: Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University Medical Center, Georgetown University, Washington, DC, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Da Cunha
authors.affiliation: Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University Medical Center, Georgetown University, Washington, DC, USA.
authors.forename: Janice D
authors.initials: JD
authors.lastname: Rone
authors.affiliation: Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University Medical Center, Georgetown University, Washington, DC, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University Medical Center, Georgetown University, Washington, DC, USA.
authors.forename: Yuriy
authors.initials: Y
authors.lastname: Gusev
authors.affiliation: Lombardi Comprehensive Cancer Center and Department of Oncology, Georgetown University Medical Center, Georgetown University, Washington, DC, USA.
authors.forename: Bassem R
authors.initials: BR
authors.lastname: Haddad
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000473:pathology*; D055088:Early Detection of Cancer; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction
chemical_list: D035683:MicroRNAs