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

Autor: Nguyen Van Long F; Cancer Research Center of Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Léon Bérard Cancer Centre, Cheney A, 28 rue Laennec, 69373 cedex 08, Lyon, France.; Institut Convergence PLAsCAN, 69373 cedex 08, Lyon, France.; DevWeCan Labex Laboratory, 69373 cedex 08, Lyon, France., Lardy-Cleaud A; Biostatistics Unit, Department of Clinical Research, Léon Bérard Cancer Centre, 28 rue Laennec, 69008, Lyon, France., Carène D; Predictive Biomarkers and Novel Therapeutic Strategies Group, Institut Gustave Roussy, University of Paris Sud, INSERM 981, Université Paris Saclay, 114 rue Edouard Vaillant, 94800, Villejuif, France.; Department of Biostatistics and Epidemiology, Institut Gustave Roussy, 94800, Villejuif, France., Rossoni C; Department of Biostatistics and Epidemiology, Institut Gustave Roussy, 94800, Villejuif, France., Catez F; Cancer Research Center of Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Léon Bérard Cancer Centre, Cheney A, 28 rue Laennec, 69373 cedex 08, Lyon, France.; Institut Convergence PLAsCAN, 69373 cedex 08, Lyon, France.; DevWeCan Labex Laboratory, 69373 cedex 08, Lyon, France., Rollet P; Cancer Research Center of Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Léon Bérard Cancer Centre, Cheney A, 28 rue Laennec, 69373 cedex 08, Lyon, France.; Institut Convergence PLAsCAN, 69373 cedex 08, Lyon, France.; DevWeCan Labex Laboratory, 69373 cedex 08, Lyon, France., Pion N; Cancer Research Center of Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Léon Bérard Cancer Centre, Cheney A, 28 rue Laennec, 69373 cedex 08, Lyon, France.; Institut Convergence PLAsCAN, 69373 cedex 08, Lyon, France.; DevWeCan Labex Laboratory, 69373 cedex 08, Lyon, France., Monchiet D; Cancer Research Center of Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Léon Bérard Cancer Centre, Cheney A, 28 rue Laennec, 69373 cedex 08, Lyon, France.; Institut Convergence PLAsCAN, 69373 cedex 08, Lyon, France.; DevWeCan Labex Laboratory, 69373 cedex 08, Lyon, France., Dolbeau A; Cancer Research Center of Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Léon Bérard Cancer Centre, Cheney A, 28 rue Laennec, 69373 cedex 08, Lyon, France.; Institut Convergence PLAsCAN, 69373 cedex 08, Lyon, France.; DevWeCan Labex Laboratory, 69373 cedex 08, Lyon, France., Martin M; Cancer Research Center of Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Léon Bérard Cancer Centre, Cheney A, 28 rue Laennec, 69373 cedex 08, Lyon, France.; Institut Convergence PLAsCAN, 69373 cedex 08, Lyon, France.; DevWeCan Labex Laboratory, 69373 cedex 08, Lyon, France., Simioni V; Cancer Research Center of Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Léon Bérard Cancer Centre, Cheney A, 28 rue Laennec, 69373 cedex 08, Lyon, France.; Institut Convergence PLAsCAN, 69373 cedex 08, Lyon, France.; DevWeCan Labex Laboratory, 69373 cedex 08, Lyon, France., Bray S; Tayside Tissue Bank, Ninewells Hospital and Medical School, NHS Tayside, Dundee, DD1 9SY, Scotland, UK., Le Beherec D; Department Translational Research, Institut Gustave Roussy, 94800, Villejuif, France., Mosele F; Predictive Biomarkers and Novel Therapeutic Strategies Group, Institut Gustave Roussy, University of Paris Sud, INSERM 981, Université Paris Saclay, 114 rue Edouard Vaillant, 94800, Villejuif, France., Bouakka I; Predictive Biomarkers and Novel Therapeutic Strategies Group, Institut Gustave Roussy, University of Paris Sud, INSERM 981, Université Paris Saclay, 114 rue Edouard Vaillant, 94800, Villejuif, France., Colombe-Vermorel A; Department of Translational Research and Innovation, Léon Bérard Cancer Centre, 28 rue Laennec, 69008, Lyon, France., Odeyer L; Department of Translational Research and Innovation, Léon Bérard Cancer Centre, 28 rue Laennec, 69008, Lyon, France., Diot A; Division of Cancer Research, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, Scotland, UK., Jordan LB; Department of Pathology, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, Scotland, UK., Thompson AM; Division of Cancer Research, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, Scotland, UK.; Olga Keith Wiess Chair of Surgery, Dan L. Duncan Breast Center, Division of Surgical Oncology, Baylor College of Medicine, Houston, TX, 77030, USA., Jamen F; Université Paris-Saclay Institute of Neuroscience, CNRS UMR9197, Gif-sur-Yvette, France.; Université Paris-Saclay, CIAMS, 91405, Orsay, Cedex, France., Dubois T; Breast Cancer Biology Group, Translational Research Department, Institut Curie-PSL Research University, 26 rue d'Ulm, 75005, Paris, France., Chabaud S; Biostatistics Unit, Department of Clinical Research, Léon Bérard Cancer Centre, 28 rue Laennec, 69008, Lyon, France., Michiels S; Department of Biostatistics and Epidemiology, Institut Gustave Roussy, 94800, Villejuif, France., Treilleux I; Department of Translational Research and Innovation, Léon Bérard Cancer Centre, 28 rue Laennec, 69008, Lyon, France., Bourdon JC; Division of Cancer Research, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, Scotland, UK., Pérol D; Biostatistics Unit, Department of Clinical Research, Léon Bérard Cancer Centre, 28 rue Laennec, 69008, Lyon, France., Puisieux A; Cancer Research Center of Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Léon Bérard Cancer Centre, Cheney A, 28 rue Laennec, 69373 cedex 08, Lyon, France.; DevWeCan Labex Laboratory, 69373 cedex 08, Lyon, France., André F; Predictive Biomarkers and Novel Therapeutic Strategies Group, Institut Gustave Roussy, University of Paris Sud, INSERM 981, Université Paris Saclay, 114 rue Edouard Vaillant, 94800, Villejuif, France., Diaz JJ; Cancer Research Center of Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Léon Bérard Cancer Centre, Cheney A, 28 rue Laennec, 69373 cedex 08, Lyon, France. jean-jacques.diaz@lyon.unicancer.fr.; Institut Convergence PLAsCAN, 69373 cedex 08, Lyon, France. jean-jacques.diaz@lyon.unicancer.fr.; DevWeCan Labex Laboratory, 69373 cedex 08, Lyon, France. jean-jacques.diaz@lyon.unicancer.fr., Marcel V; Cancer Research Center of Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Léon Bérard Cancer Centre, Cheney A, 28 rue Laennec, 69373 cedex 08, Lyon, France. virginie.marcel@lyon.unicancer.fr.; Institut Convergence PLAsCAN, 69373 cedex 08, Lyon, France. virginie.marcel@lyon.unicancer.fr.; DevWeCan Labex Laboratory, 69373 cedex 08, Lyon, France. virginie.marcel@lyon.unicancer.fr.
Jazyk: angličtina
Zdroj: BMC cancer [BMC Cancer] 2022 May 11; Vol. 22 (1), pp. 526. Date of Electronic Publication: 2022 May 11.
DOI: 10.1186/s12885-022-09552-x
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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