Evaluation of novel diagnostic and prognostic miRNA signatures in triple negative breast cancer

Introduction: We focus on the expression analysis of non-coding microRNAs (miRNAs) with regulatory functions in breast cancer (BC), especially on the intrinsic subgroup characterized as triple negative (TNBC). Objective of the interdisciplinary collaboration is the establishment of a distinct miRNA signature panel as a diagnostic and prognostic tool in TNBC management.

Methods: Retrospective miRNA expression study was performed, consisting of 47 formalin-fixed-paraffin-embedded and immunohistochemically re-classified TNBC. 23 TNBC were immunohistochemically identified as basal-like and 24 as TNBC only. After micro-dissection, quantitative expression analysis (RTqPCR) was performed for 18 miRNAs (15 non-coding miRNAs and three miRNA housekeepers). Results of quantitative expression analysis were statistically correlated with routine pathological parameters using SPSS 21.0.

Results: Specific subsets of miRNA expression signatures in regard to intrinsic tumor subtyping for miRNA 16 (p < 0.0001), miRNA 26b (p < 0.0001), miRNA 10b (p = 0.012), miRNA 19b (p < 0.0001), miRNA 200c (p < 0.011) and miRNA 200b (p = 0.047) were identified. Furthermore, statistical significant correlations between miRNA 155 expression and overall survival (p = 0.010) as well as a statistical trend for miRNA 206 (p = 0.123) were found. Aside to the conventional pathological UICC parameters for nodal (p = 0.019) and distance metastases (p < 0.0001), multivariate analysis revealed miRNA 155 (p < 0.0001) as an independent prognosticator.

Conclusion: Preliminary data assessment points out auspicious miRNA expression pattern that hold high validity to prove as useful and specific sub-classification tool and prognosticator in TNBC breast cancer diagnosis with a potential indicatory value for clinical treatment options. For data-consolidation, additional TNBC cohorts from DKTK partner-sides have been recruited.