title: Overexpression of microRNA-200c predicts poor outcome in patients with PR-negative breast cancer.
abstract: Micro-RNAs are small, noncoding RNAs that act as tumor suppressors or oncogenes. MiR-200c is a member of the miR-200 family; it is known to be dysregulated in invasive breast carcinoma. MiR-200c maintains the epithelial-mesenchymal transition and inhibits cell migration and invasion. Recent studies showed that miR-200c regulated steroid hormone receptors, estrogen receptors (ER), and progesterone receptors (PR). The present study aimed to detect miR-200c in 172 invasive breast carcinoma cases selected from a prospective cohort enrolled in Kuopio, Eastern Finland, between 1990 and 1995. MiR-200c expression was determined with relative q-PCR, and results were compared to clinicopathological variables and patient outcome. We found that PR status combined with miR-200c expression was a significant marker of outcome. High miR-200c expression was associated with reduced survival in PR-negative cases (n = 68); low miR-200c expression indicated reduced survival in PR-positive cases (n = 86) (Cox regression: P = 0.002, OR = 3.433; and P = 0.004, OR = 4.176, respectively). In PR-negative cases, high miR-200c expression was associated with shortened relapse-free survival (Cox regression: P = 0.001, OR = 3.613); increased local/distant recurrence (Logistic regression: P = 0.006, OR = 3.965); and more frequent distant metastasis (Logistic regression: P = 0.015, OR = 3.390). We also found that high grade and low stage tumors were positively correlated with high miR-200c expression (Logistic regression for high grade tumors: P = 0.002, OR = 2.791 and for high stage tumors: P = 0.035, OR = 0.285). Our results indicated that miR-200c may play a role in invasive breast carcinoma. Furthermore, miR-200c combined with PR status provided a refined predictor of outcome. In future, a larger study is required to confirm our results. This data may provide a basis for new research target-progesterone receptor-regulated microRNAs in breast cancer.
authors.affiliation: Institute of Clinical Medicine, Clinical Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Marie
authors.initials: M
authors.lastname: Tuomarila
authors.affiliation: Institute of Clinical Medicine, Clinical Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Kaisa
authors.initials: K
authors.lastname: Luostari
authors.affiliation: Institute of Clinical Medicine, Clinical Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Ylermi
authors.initials: Y
authors.lastname: Soini
authors.affiliation: Institute of Clinical Medicine, Oncology, University of Eastern Finland, Kuopio, Finland.
authors.forename: Vesa
authors.initials: V
authors.lastname: Kataja
authors.affiliation: Institute of Clinical Medicine, Clinical Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Veli-Matti
authors.initials: VM
authors.lastname: Kosma
authors.affiliation: Institute of Clinical Medicine, Clinical Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Arto
authors.initials: A
authors.lastname: Mannermaa
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D011980:Receptors, Progesterone