Combined analysis of miR-200 family and its significance for breast cancer

Abstract

While the molecular functions of miR-200 family have been deeply investigated, a role for these miRNAs as breast cancer biomarkers remains largely unexplored. In the attempt to clarify this, we profiled the miR-200 family members expression in a large cohort of breast cancer cases with a long follow-up (H-CSS cohort) and in TCGA-BRCA cohort. Overall, miR-200 family was found upregulated in breast tumors with respect to normal breast tissues while downregulated in more aggressive breast cancer molecular subtypes (i.e. Luminal B, HER2 and triple negative), consistently with their function as repressors of the epithelial-to-mesenchymal transition (EMT). In particular miR-141-3p was found differentially expressed in breast cancer molecular subtypes in both H-CSS and TCGA-BRCA cohorts, and the combined analysis of all miR-200 family members demonstrated a slight predictive accuracy on H-CSS cancer specific survival at 12 years (survival c-statistic: 0.646; 95%CI 0.538-0.754).

Figure 1

miR-200 family members expression in H-CSS cohort in tumor tissues (T), normal breast tissues distant from tumor (M) and normal breast tissue from reductive mammoplasty (NBT). Plots were performed using the R Foundation for Statistical Computing (version 3.6, packages: ggplot2, gridExtra).

Figure 2

miR-200 family members expression in TCGA-BRCA cohort in tumor tissues (T), and normal breast tissues distant from tumor (N). Plots were performed using the R Foundation for Statistical Computing (version 3.6, packages: ggplot2, gridExtra).

Figure 3

miR-200 family members expression within the surrogate molecular classification subgroups identified in the H-CSS cohort: HER2 amplified tumors (HER2), Luminal A (LUMA), Luminal B (LUMB), Triple Negative (TNEG). Plots were performed using the R Foundation for Statistical Computing (version 3.6, packages: ggplot2, gridExtra).

Figure 4

miR-200 family members differential expression within the intrinsic molecular classification subgroups in the TCGA-BRCA cohort: HER2 enriched tumors (HER2), Luminal A (LUMA), Luminal B (LUMB), Basal like, and NORMAL LIKE tumors. Plots were performed using the R Foundation for Statistical Computing (version 3.6, packages: ggplot2, gridExtra).

Figure 5

Forest plot of hazard ratios (HR) for studies on plasma samples from breast cancer patients. Plots were performed using the R Foundation for Statistical Computing (version 3.6, packages: ggplot2, gridExtra).