Molecular MicroRNA Signatures of Breast Cancer with Brain Metastasis
Seema Sethi, Aamir Ahmad, Rouba Ali-Fehmi, Sandeep Mittal, Wei Chen, Fazlul H Sarkar. Wayne State University School of Medicine, Detroit, MI
Background: Breast cancer is the most common non-skin cancer among women in the US. Breast cancer-related mortality and morbidity are primarily due to metastatic disease especially brain metastasis which also impacts patients' quality of life. Molecular mechanisms of brain metastasis of breast cancer is largely unknown. Molecular signatures in the primary breast cancers that identify prediliction for brain metastasis would be very important for prognosis and designing novel targetted therapies to prevent and eliminate brain metastasis. MicroRNAs (miRNAs) are recently described novel molecules with great promise in this regard.
Design: RNA was extracted from formalin fixed paraffin embedded tumor tissues from a cohort of breast cancer patients with brain metastasis, and age, stage and follow-up matched breast cancer cases without brain metastasis. We interogated microRNA expression status by profiling using EQIXON assay. Quantitative real-time PCR (qRT-PCR) was used to validate abnormal expression of miRNAs. Data was statistically analyzed using Kruskal-Wallis test to determine the clinical significance of the findings.
Results: Of the over 120 microRNAs profiled, expression of microRNA miR-10b was highly increased in the primary breast cancers of patients who subsequently developed brain metastasis as compared to those who did not develop brain metastasis. The miR-10b expression was reduced in the metastatic brain tumors as compared to primary breast cancer tumors. Statistical analysis using the Kruskal-Wallis test across all 3 groups was significant (p < 0.001).
Conclusions: MicroRNA miR-10b was significantly increased in the primary breast cancers which metastasized to the brain. Its espression was reduced in the metastatic brain tumors indicating 'homing' effect. Our findings are clinically relevant since they have potential clinical use in prognosis and targetted anti-metastatic therapy in breast cancer patients. MicroRNA miR-10b could be silenced by antagomirs (chemically modified anti-miRNA oligonucleotides) to treat and prevent brain metastasis. These molecular microRNA signature-based prophylactic and therapeutic strategies could improve patients' quality of life and overall survival in the era of personalized medicine.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 38, Monday Morning