You are viewing the site in preview mode

Skip to main content

Advertisement

Systems biology analysis of gene expression data and gene network reverse-engineering approaches reveal NFAT5 as a candidate biomarker in Inflammatory Breast Cancer

Article metrics

  • 891 Accesses

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.

References

  1. 1.

    Levine PH, Steinhorn SC, Ries LG, Aron JL: Inflammatory breast cancer: the experience of the Surveillance, Epidemiology and End Results (SEER) Program. J Natl Cancer Inst. 1985, 74: 291-297.

  2. 2.

    Cristofanilli M, Valero V, Buzdar AU, Kau SW, Broglio KR, Gonzalez-Angulo AM, Sneige N, Islam R, Ueno NT, Buchholz TA, Singletary SE, Hortobagyi GN: Inflammatory breast cancer (IBC) and patterns of recurrence: understanding the biology of a unique disease. Cancer. 2007, 110 (7): 1436-1444. 10.1002/cncr.22927.

  3. 3.

    Charafe-Jauffret E, Tarpin C, Viens P, Bertucci F: Defining the molecular biology of inflammatory breast cancer. Semin Oncol. 2008, 35 (1): 41-50. 10.1053/j.seminoncol.2007.11.015.

  4. 4.

    Manfrin E, Remo A, Pancione M, Cannizzaro C, Falsirollo F, Pollini GP, Pellini F, Molino A, Vendraminelli R, Ceccarelli M, Pagnotta SM, Simeone I, Bonetti F: Comparison between invasive breast cancer with extensive peritumoral vascular invasion and inflammatory breast carcinoma. A clinical pathological study of 161 cases. Am J Clin Pathol. 2014, 142 (3): 299-306. 10.1309/AJCPOXKX67KRAOVM.

  5. 5.

    Bekhouche I, Finetti P, Adelaïde J, Ferrari A, Tarpin C, Charafe-Jauffret E, Charpin C, Houvenaeghel G, Jacquemier J, Bidaut G, Birnbaum D, Viens P, Chaffanet M, Bertucci F: High-resolution comparative genomic hybridization of inflammatory breast cancer and identification of candidate genes. PLoS One. 2011, 6 (2): e16950-10.1371/journal.pone.0016950.

  6. 6.

    Margolin AA, Nemenman I, Basso K, Wiggins C, Stolovitzky G, DallaFavera R, Califano A: ARACNE: an algorithm for the reconstruction of gene regulatory networks in a mammalian cellular context. BMC Bioinformatics. 2006, 7 (Suppl 1): S7-10.1186/1471-2105-7-S1-S7.

  7. 7.

    Carro MS, Lim WK, Alvarez MJ, Bollo RJ, Zhao X, Snyder EY, Sulman EP, Anne SL, Doetsch F, Colman H, Lasorella A, Aldape K, Califano A, Iavarone A: The transcriptional network for mesenchymal transformation of brain tumours. Nature. 2010, 463 (7279): 318-25. 10.1038/nature08712.

Download references

Author information

Correspondence to Michele Ceccarelli.

Additional information

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

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Keywords

  • Breast Cancer
  • Lymphovascular Invasion
  • Inflammatory Breast Cancer
  • Normal Breast Tissue
  • Metastatic Form