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Systems biology analysis of gene expression data and gene network reverse-engineering approaches reveal NFAT5 as a candidate biomarker in Inflammatory Breast Cancer
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  1. Andrea Remo1,
  2. Ines Simeone2,
  3. Massimo Pancione3,
  4. Pietro Parcesepe4,
  5. Pascal Finetti5,
  6. Halima Bensmail2,
  7. Luigi Cerulo3,
  8. Vittorio Colantuoni3,
  9. Daniel Birnbaum5,
  10. Franco Bonetti4,
  11. Francois Bertucci5,
  12. Erminia Manfrin4 and
  13. Michele Ceccarelli2
  1. Aff1 Department of PathologyMater Salutis Hospital Legnago Italy
  2. Aff2 grid.418818.c0000000105162170Qatar Computing Research Institute (QCRI)Qatar Foundation Doha Qatar
  3. Aff3 grid.47422.370000000107243038Department of Science and TechnologyUniversity of Sannio Benevento Italy
  4. Aff4 grid.5611.30000000417631124Department of Pathology and DiagnosisUniversity of Verona Verona Italy
  5. Aff5 grid.418443.e0000000405984440Department of Molecular OncologyInstitut Paoli-Calmettes U1068 Inserm Marseille France

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Meeting abstracts

Inflammatory Breast Cancer (IBC) is the most aggressive and highly metastatic form of breast cancer [13]. In a recent study [4], we analysed breast cancer with peritumoral neoplastic lymphovascular invasion (ePVI) in comparison with inflammatory breast cancer, showing that ePVI breast cancer have more clinicopathologic affinity than differences with the most aggressive cancer in the breast. Here, we aim to identify potential master regulators (MRs) that drive the expression pattern in IBC.

Transcriptomic (i.e., mRNA) data from 197 breast tumours were used for this analysis (GEO GSE23720) [5]. All tumours were classified as “IBC” (n=63) or “nIBC” (n=134). To identify novel MRs that drive the IBC phenotype, all expression data were analysed using a network-based strategy (ARACNe [6]) and Master Regulator Analysis (MRA)[7]. We chose to perform in-vivo IHC analysis, in two independent cohorts of IBCs (n = 39), nIBCs (n = 82) and normal breast tissues (n = 15), for the top significant Master Regulators: MGA, CTNNB1 and NFAT5. Biological validation confirmed that NFAT5 expression was higher in IBC than in nIBC (70% vs. 20%) and that the majority of NFAT5-positive IBC samples displayed NFAT5 nuclear expression in comparison with nIBC samples (89% vs. 12%).

We provide evidence that NFAT5 transcription factor could constitute a novel IBC biomarker that could help to identify the most aggressive forms of BC into routine clinical practice.

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Footnotes

  • Andrea Remo, Ines Simeone, Massimo Pancione and Michele Ceccarelli contributed equally to this work.