MicroRNAs Predict Likelihood of Breast Cancer Metastasis

The discovery that breast cancer patients who experienced quick relapses tended to have low levels of the microRNA miR-21 and high levels of the microRNA miR-205 in their tumor tissues suggests that measurement of these two biomarkers could identify women at risk of metastasis.

The stability of microRNAs (miRNAs)—snippets of about 20 nucleotides that block gene expression by attaching to molecules of messenger RNA (mRNA) in a fashion that prevents them from transmitting the protein synthesizing instructions they had received from the DNA—in formalin-fixed paraffin-embedded (FFPE) tissues enables their reliable analysis in archived FFPE tissue samples. Such samples are an invaluable source in the search for novel biomarkers. This is especially true in the case of breast cancer, for which late relapses occur in many cases. Thus, analysis of miRNAs in FFPE breast tumor samples holds great potential, as this type of testing can lead to the discovery of novel biomarkers suitable for future routine clinical diagnostics.

Investigators at the University of Athens (Greece) investigated the prognostic significance of six metastasis-related miRNAs that regulate various stages of migration and invasion and play critical roles in the multistep metastatic process. They quantified the expression of miR-21, miR-205, miR-10b, miR-210, miR-335, and let-7a by reverse-transcription quantitative PCR in FFPE tissues from 84 patients with early breast cancer and a long follow-up, and 13 cancer-free breast tissue FFPE samples that were used as the control group. They further correlated individual miRNA over- or under-expression with the disease-free interval (DFI) and overall survival (OS).

Results published in the January 2014 issue of the journal Clinical Chemistry revealed that that both miR-21 and miR-205 were significantly associated with DFI and only miR-205 with OS. Multivariate analysis demonstrated that miR-205 and miR-21 were independent factors associated with early disease relapse, whereas only miR-205 overexpression was associated with OS.

The authors concluded that, "Our results clearly indicate that deregulation of metastasis-associated miRNAs in primary tumors is associated with clinical outcome in patients with early breast cancer and can differentiate patients with higher risk in well-characterized subgroups."

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