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).

Highlights

  • While the molecular functions of miR-200 family have been deeply investigated, a role for these miRNAs as breast cancer biomarkers remains largely unexplored

  • Metastases at diagnosis were present in 16 cases; among non-metastatic patients (N = 271), 55 experienced disease progression (Incidence Rate, IR of 3.5 events per 100 person-years), and 30 of them died for the disease (IR of 1.7 events per 100 person-years)

  • Tumors were defined as cases expressing estrogen (ER) or progesterone (PgR) receptors in ≥ 1% of neoplastic cells as indicated by international ­guidelines[8], and HER2 status assessment was carried out according to standard ­recommendations[9]

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Summary

Introduction

While the molecular functions of miR-200 family have been deeply investigated, a role for these miRNAs as breast cancer biomarkers remains largely unexplored. Category Mean ± SD Median (IQR) Range Mean ± SD Median (IQR) Range Mean ± SD Median (IQR) Range Primitive Recurrence No Yes NST NST + ILC ILC Bilateral Right Left Stage I Stage IIa Stage IIb Stage IIIa Stage IIIb Stage IIIc Stage IV Missing values 1 2 3 Negative Positive Negative Positive Missing values AMP NEG Missing values HER2-amplified Luminal A-like Luminal B-like Triple Negative These contrasting results led us to perform an extensive expression analysis of the entire miR-200 family in two large cohorts of breast cancer patients, the first collected in our hospital (H-CSS cohort, N = 283) and the second from The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA cohort, N = 451), in order to clarify the extent of miR-200 family deregulation in breast cancer, and its specific association with clinicopathological parameters

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