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Thursday, February 14, 2013

MicroRNA profiles in breast cancer

In order to successfully treat cancer, it’s critical to identify the exact type of tumor afflicting the patient. This is not only important for providing the correct treatment, but also for avoiding wasting patients’ time with inappropriate treatments. Case in point: triple negative breast cancer (TNBC).

Breast cancers are classified in part by the type of receptors they express. TNBC tumors do not express any of the three most common receptors: estrogen, progesterone or Her2. Not only do TNBCs not respond to the types of treatment that non-TNBC tumors do, but there are many TNBC subgroups that each require a different protocol. Clearly, the sooner TNBCs can be identified and categorized, the better.

Kay Huebner from the Ohio State University and her colleagues have found a way to distinguish TNBCs that relies on the pattern of microRNAs (miRNAs) produced. These are tiny snippets of RNA, no more than 25 nucleotides long, that affect gene expression by binding to messenger RNA is specific places. Because TNBCs are, by definition, deficient in receptor expression, the researchers thought that there could be specific miRNAs targeting those gene sequences. This is exactly what they found.

When the scientists compared miRNAs in TNBC tumor cells versus non-tumor cells from the same women, there were about a dozen of these nucleotide fragments that were altered. In some cases the tumor cells had more of the particular miRNA, in others less of it.

The researchers also determined the miRNA profile of metastatic tumors found in the lymph nodes of the same women. Presumably, these tumors were derived from the original TNBC tumor within the breast tissue. Nevertheless there were a few differences in the miRNA profile between the lymph lesions and the TNBC or normal tissues. This may lead to insights into the metastasis process.

Overall, the scientists were able to develop two miRNA ‘signatures’ or patterns of upregulated and downregulated miRNA. Patients with one combination of miRNAs had far better long-term outcomes than those with the second, riskier pattern. The authors suggest that doctors consider more aggressive therapies for such patients.

Cascione, L., Gasparini, P., Lovat, F., Carasi, S., Pulvirenti, A., Ferro, A., Alder, H., He, G., Vecchione, A., Croce, C., Shapiro, C., & Huebner, K. (2013). Integrated MicroRNA and mRNA Signatures Associated with Survival in Triple Negative Breast Cancer PLoS ONE, 8 (2) DOI: 10.1371/journal.pone.0055910.