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Search: id:"swepub:oai:lup.lub.lu.se:df6e70b2-7f64-486c-aee5-9de85d220230" > Delineating Transcr...

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  • Lanigan, Fiona (author)

Delineating Transcriptional Networks of Prognostic Gene Signatures Refines Treatment Recommendations for Lymph Node-negative Breast Cancer Patients.

  • Article/chapterEnglish2015

Publisher, publication year, extent ...

  • 2015-07-14
  • Wiley,2015

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:df6e70b2-7f64-486c-aee5-9de85d220230
  • https://lup.lub.lu.se/record/7484353URI
  • https://doi.org/10.1111/febs.13354DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • The majority of women diagnosed with lymph node-negative breast cancer are unnecessarily treated with damaging chemotherapeutics following surgical resection. This highlights the importance of understanding and more accurately predicting patient prognosis. Here, we define the transcriptional networks regulating well-established prognostic gene expression signatures. We find that the same set of transcriptional regulators consistently lie upstream of both 'prognosis' and 'proliferation' gene signatures, suggesting that a central transcriptional network underpins a shared phenotype within these signatures. Strikingly, the master transcriptional regulators within this network predict recurrence risk for lymph node-negative breast cancer better than currently used multi-gene prognostic assays, particularly in lymph node-negative, estrogen receptor-positive patients. Simultaneous examination of p16(INK) (4A ) expression, which predicts tumors that have bypassed cellular senescence, revealed that intermediate levels of p16(INK) (4A) correlate with an intact pRB pathway and improved survival. A combination of these master transcriptional regulators and p16(INK) (4A) , termed the OncoMasTR score, stratifies tumours based on their proliferative and senescence capacity, facilitating a clearer delineation of lymph node-negative breast cancer patients at high risk of recurrence, and thus requiring chemotherapy. Furthermore, OncoMasTR accurately classifies over 60% of patients as 'low risk', an improvement on existing prognostic assays, which has the potential to reduce overtreatment in early-stage patients. Taken together, this study provides new insights into the transcriptional regulation of cellular proliferation in breast cancer and provides an opportunity to enhance and streamline breast cancer prognosis. This article is protected by copyright. All rights reserved.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Brien, Gerard L (author)
  • Fan, Yue (author)
  • Madden, Stephen F (author)
  • Jerman, Emilia (author)
  • Aloraifi, Fatima (author)
  • Hokamp, Karsten (author)
  • Dunne, Eiseart J (author)
  • Lohan, Amanda J (author)
  • Flanagan, Louise (author)
  • Garbe, James C (author)
  • Stampfer, Martha R (author)
  • Fridberg, MarieLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Institutionen för translationell medicin,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Department of Translational Medicine(Swepub:lu)mikr-mfr (author)
  • Jirström, KarinLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)pat-kji (author)
  • Quinn, Cecily M (author)
  • Loftus, Brendan (author)
  • Gallagher, William M (author)
  • Geraghty, James (author)
  • Bracken, Adrian P (author)
  • TumörmikromiljöSektion I (creator_code:org_t)

Related titles

  • In:The FEBS Journal: Wiley282:18, s. 3455-34731742-464X

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