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.
Highlights
Breast cancer is a heterogeneous disease with subtypes characterized by many different biological and clinical features
High miR-200c expression correlates with grade 3 tumors First, the relative miR-200c expression rates were compared with the clinicopathological variables of the 172 invasive breast carcinoma samples
High miR-200c expression was associated with grade 3 tumors (P = 0.002, Table 1) and with low stage cancers (P = 0.045, Table 1)
Summary
Breast cancer is a heterogeneous disease with subtypes characterized by many different biological and clinical features. The disease prognosis varies with the subtype and other clinical markers [1,2,3]. Immunohistochemical studies are routinely conducted to detect molecular markers that identify different subtypes. These markers include the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her2), and Ki-67 labeling index. The detection of these markers facilitates diagnosing and planning the appropriate therapy [4]. Novel diagnostic methods and better factors for predicting risk are needed to extend our understanding of breast cancer and to develop new therapeutic methods for combating cancer
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