Low level of Fibrillarin, a ribosome biogenesis factor, is a new independent marker of poor outcome in breast cancer

Flora Nguyen Van Long, Audrey Lardy-Cleaud, Dimitri Carène, Caroline Rossoni, Frédéric Catez, Paul Rollet, Nathalie Pion, Déborah Monchiet, Agathe Dolbeau, Marjorie Martin, Valentin Simioni, Susan Bray, Doris Le Beherec, Fernanda Mosele, Ibrahim Bouakka, Amélie Colombe-Vermorel, Laetitia Odeyer, Alexandra Diot, Lee B. Jordan, Alastair M. ThompsonFrançoise Jamen, Thierry Dubois, Sylvie Chabaud, Stefan Michiels, Isabelle Treilleux, Jean-Christophe Bourdon, David Pérol, Alain Puisieux, Fabrice André, Jean-Jacques Diaz (Lead / Corresponding author), Virginie Marcel (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)
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Abstract

Background: A current critical need remains in the identification of prognostic and predictive markers in early breast cancer. It appears that a distinctive trait of cancer cells is their addiction to hyperactivation of ribosome biogenesis. Thus, ribosome biogenesis might be an innovative source of biomarkers that remains to be evaluated.

Methods: Here, fibrillarin (FBL) was used as a surrogate marker of ribosome biogenesis due to its essential role in the early steps of ribosome biogenesis and its association with poor prognosis in breast cancer when overexpressed. Using 3,275 non-metastatic primary breast tumors, we analysed FBL mRNA expression levels and protein nucleolar organisation. Usage of TCGA dataset allowed transcriptomic comparison between the different FBL expression levels-related breast tumours.

Results: We unexpectedly discovered that in addition to breast tumours expressing high level of FBL, about 10% of the breast tumors express low level of FBL. A correlation between low FBL mRNA level and lack of FBL detection at protein level using immunohistochemistry was observed. Interestingly, multivariate analyses revealed that these low FBL tumors displayed poor outcome compared to current clinical gold standards. Transcriptomic data revealed that FBL expression is proportionally associated with distinct amount of ribosomes, low FBL level being associated with low amount of ribosomes. Moreover, the molecular programs supported by low and high FBL expressing tumors were distinct.

Conclusion: Altogether, we identified FBL as a powerful ribosome biogenesis-related independent marker of breast cancer outcome. Surprisingly we unveil a dual association of the ribosome biogenesis FBL factor with prognosis. These data suggest that hyper- but also hypo-activation of ribosome biogenesis are molecular traits of distinct tumors.

Original languageEnglish
Article number526
Pages (from-to)1-12
Number of pages12
JournalBMC Cancer
Volume22
DOIs
Publication statusPublished - 11 May 2022

Keywords

  • Biomarkers/metabolism
  • Breast Neoplasms/genetics
  • Chromosomal Proteins, Non-Histone
  • Female
  • Humans
  • RNA, Messenger/genetics
  • Ribosomes/genetics
  • rRNA 2’O-ribose methylation complex
  • Ribosome biogenesis
  • Fibrillarin
  • AgNOR
  • Breast cancer

ASJC Scopus subject areas

  • Genetics
  • Oncology
  • Cancer Research

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