Abstract 5332: MicroRNA profile of triple-negative breast cancer and prognosis.
Authors: Yoshimatsu Toshio F. , Yao Katharine , Kaul Karen , Turk Mary A. , Olopade Olufunmilayo I. , Huo Dezheng 
Published: August 2014

Background: Triple-negative breast cancer (TNBC, estrogen receptor [ER]-, progesterone receptor [PR]-, and human epidermal growth factor receptor 2 [HER2]-negative) is often aggressive and lack molecular targets for therapy. As gene regulators, microRNAs (miRNA) are important in cancer etiology but their utility as tumor biomarkers for cancer diagnosis and prognosis is yet unclear.

Methods: To characterize the differential expression pattern of miRNA in TNBC from non-TNBC, we performed a whole miRNome profiling using TaqMan based quantitative PCR array of 754 miRNAs constructed based on miRBase 19 (Life Technologies, CA). Total RNA was extracted from frozen breast tumors and only RNA samples with good quality were included in the array experiment. Rigorous post-experiment quality controls were further conducted to remove unreliable plates. Moderate t-test was used to identify TNBC-specific miRNAs and Cox proportional hazard model was used to explore miRNAs that predict progression-free survival. Benjamini and Hochberg's false discovery rate method was used to correct for multiple testing.

Results: Samples from 85 patients were included in the final analysis, including 71 Caucasians, 7 African Americans, and 7 others. The average age (±SD) was 54.9 ± 9.1 years. 17 patients had stage 1 tumor, 30 stage 2A, 26 stage 2B, 7 stage 3A, and 5 stage 3B. There were 42 samples with ER+, 37 PR+, 25 HER2+, and 25 categorized as TNBC. 363 out of 754 miRNAs showed expression in at least half of the samples and were included for further analysis. Of the 363 miRNAs, we found 98 to be significantly different between TNBC and non-TNBC after multiple testing correction. The most significant miRNA (miR-190b) was down-regulated in TNBC by about 20-fold (p=1.6x10-9). In fact, most of these miRNAs are down-regulated in TNBC compared to non-TNBC. During a median follow-up of 10.9 years, 29 patients died and 7 patients survived but had progressive disease of breast cancer. After multiple testing correction, we found 6 miRNAs showing significant association with progression-free survival. Interestingly, none of these 6 miRNAs were related to TNBC, suggesting that their prognostic value is independent of breast cancer subtypes.

Conclusion: Our study demonstrates the existence of a set of miRNAs specific to TNBC, which has a clear “fingerprint” to differentiate TNBC from non-TNBC. We also identified different set of miRNAs that could serve as prognostic markers. Despite the small sample set, our results promisingly indicate the potential of miRNA as diagnostic and prognostic tool for breast cancer. A replication study with larger sample size would be in order.

Citation Format: Toshio F. Yoshimatsu, Katharine Yao, Karen Kaul, Mary A. Turk, Olufunmilayo I. Olopade, Dezheng Huo. MicroRNA profile of triple-negative breast cancer and prognosis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5332. doi:10.1158/1538-7445.AM2013-5332