title: Role of miR-139 as a surrogate marker for tumor aggression in breast cancer.
abstract: MicroRNAs are non-protein coding molecules that play a key role in oncogenesis, tumor progression, and metastasis in many types of malignancies including breast cancer. In the current study, we studied the expression of microRNA-139-5p (miR-139) in invasive ductal carcinoma (IDC) of the breast and correlated its expression with tumor grade, molecular subtype, hormonal status, human epidermal growth factor receptor 2 status, proliferation index, tumor size, lymph node status, patient's age, and overall survival in 74 IDC cases. In addition, we compared and correlated miR-139 expression in 18 paired serum and tissue samples from patients with IDC to assess its value as a serum marker. Our data showed that miR-139 was down-regulated in all tumor tissue samples compared with control. More pronounced down-regulation was seen in tumors that were higher grade, estrogen receptor negative, progesterone receptor negative, more proliferative, or larger in size (P < .05). Although not statistically significant, lower miR-139 level was frequently associated with human epidermal growth factor receptor 2 overexpression. In addition, significantly lower miR-139 tissue level was seen in patients who were deceased (P = .027), although older age (>50 years) and positive local nodal disease did not adversely affect miR-139 expression. In contrast, serum miR-139 profile of the patients appeared similar to that of normal control. In conclusion, our study demonstrated that down-regulation of miR-139 was associated with aggressive tumor behavior and disease progression in breast cancer. miR-139 may serve as a risk assessment biomarker in tailoring treatment options.
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS 66160.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Dai
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS 66160.
authors.forename: Dan
authors.initials: D
authors.lastname: Gallagher
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS 66160.
authors.forename: Sarah
authors.initials: S
authors.lastname: Schmitt
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS 66160.
authors.forename: Ziyan Y
authors.initials: ZY
authors.lastname: Pessetto
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS 66160.
authors.forename: Fang
authors.initials: F
authors.lastname: Fan
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS 66160.
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Godwin
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, KS 66160. Electronic address: otawfik@kumc.edu.
authors.forename: Ossama
authors.initials: O
authors.lastname: Tawfik
mesh_terms: D014408:Biomarkers, Tumor / Q000145:classification / Q000235:genetics*; D001706:Biopsy; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D049109:Cell Proliferation; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D010641:Phenotype; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D016019:Survival Analysis; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; C555098:MIRN139 microRNA, human; D035683:MicroRNAs
keywords: Breast cancer; Invasive ductal carcinoma; Micro RNA; MicroRNA-139; Oncogenesis; Tumor progression