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Overexpression of MicroRNA-200c Predicts Poor Outcome in Patients with PR-Negative Breast Cancer

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  • Marie Tuomarila
  • Kaisa Luostari
  • Ylermi Soini
  • Vesa Kataja
  • Veli-Matti Kosma
  • Arto Mannermaa

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.

Suggested Citation

  • Marie Tuomarila & Kaisa Luostari & Ylermi Soini & Vesa Kataja & Veli-Matti Kosma & Arto Mannermaa, 2014. "Overexpression of MicroRNA-200c Predicts Poor Outcome in Patients with PR-Negative Breast Cancer," PLOS ONE, Public Library of Science, vol. 9(10), pages 1-8, October.
    • Handle: RePEc:plo:pone00:0109508
    DOI: 10.1371/journal.pone.0109508
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    1. Charles M. Perou & Therese Sørlie & Michael B. Eisen & Matt van de Rijn & Stefanie S. Jeffrey & Christian A. Rees & Jonathan R. Pollack & Douglas T. Ross & Hilde Johnsen & Lars A. Akslen & Øystein Flu, 2000. "Molecular portraits of human breast tumours," Nature, Nature, vol. 406(6797), pages 747-752, August.
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    1. Jianchun Wu & Zhihong Fang & Jing Xu & Weikang Zhu & Yan Li & Yongchun Yu, 2015. "Prognostic Value and Clinicopathology Significance of MicroRNA-200c Expression in Cancer: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 10(6), pages 1-13, June.

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