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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).
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1 UO di Biostatistica, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
2 Fondazione IRCCS Casa Sollievo della Sofferenza, Laboratorio Di Oncologia, San Giovanni Rotondo, Italy (GRID:grid.413503.0) (ISNI:0000 0004 1757 9135)
3 Fondazione IRCCS Casa Sollievo della Sofferenza, Cancer Biomarkers Lab, ISBREMIT, Institute for Stem-Cell Biology, Regenerative Medicine and Innovative Therapies, San Giovanni Rotondo, Italy (GRID:grid.413503.0) (ISNI:0000 0004 1757 9135)
4 UO di Oncologia, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy (GRID:grid.413503.0)
5 UO di Anatomia Patologica, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy (GRID:grid.413503.0)
6 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy (GRID:grid.419563.c) (ISNI:0000 0004 1755 9177)
7 UO di Chirurgia Senologica, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy (GRID:grid.419563.c)
8 UO di Anatomia Patologica, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy (GRID:grid.419563.c)
9 UO di Oncologia, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy (GRID:grid.419563.c)
10 UO di Biostatistica, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy (GRID:grid.419563.c)
11 Josep Carreras Leukaemia Research Institute (IJC), Badalona, Barcelona, Spain (GRID:grid.429289.c); Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain (GRID:grid.413448.e) (ISNI:0000 0000 9314 1427); University of Barcelona, Physiological Sciences Department, School of Medicine and Health Sciences, Barcelona, Spain (GRID:grid.5841.8) (ISNI:0000 0004 1937 0247); Institució Catalana de Recerca I Estudis Avançats (ICREA), Barcelona, Spain (GRID:grid.425902.8) (ISNI:0000 0000 9601 989X)