Identification of potential biomarkers for giant cell tumor of bone using comparative proteomics analysis

Amalia Conti, Gemma Caballero Rodriguez, Antonella Chiechi, Rosa Maria Dégano Blazquez, Victoria Barbado, Tibor Krènacs, Chiara Novello, Laura Pazzaglia, Irene Quattrini, Licciana Zanella, Piero Picci, Enrique De Alava, Maria Serena Benassi

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Giant cell tumor of bone can be locally aggressive and occasionally can metastasize in the lungs. To identify new markers predictive of aggressive behavior, we analyzed five patients who developed lung metastasis and five who remained disease free for a minimum of 5 years. Using two-dimensional electrophoresis, we detected 28 differentially expressed spots. Fourteen spots were identified using mass spectrometry, including seven up-regulated and seven down-regulated in metastatic samples and classified according to functional categories. We then selected five proteins involved in cell cycle or apoptosis. Thioredoxin peroxidase, allograft inflammatory factor 1, and ubiquitin E2N had more than threefold up-regulation; glutathione peroxidase 1 had 1.9-fold up-regulation; and heat shock protein 27 showed down-regulation in metastatic samples with a very low P value. After validation and analysis of protein levels, evaluation of clinical impact was assessed in a much wider cohort of primary archival specimens. Immunodetection showed a higher frequency of thioredoxin peroxidase, allograft inflammatory factor 1, ubiquitin E2N, and glutathione peroxidase 1 overexpression in primary tumors that developed into lung metastases or that locally relapsed than in the disease-free group, with variable stain intensity and distribution. Kaplan-Meier analysis showed that high expression of glutathione peroxidase 1 was strongly related to local recurrence and metastasis, suggesting that its up-regulation may identify a subset of high-risk patients with giant cell tumor prone to receive diverse clinical management.

Original languageEnglish
Pages (from-to)88-97
Number of pages10
JournalAmerican Journal of Pathology
Volume178
Issue number1
DOIs
Publication statusPublished - Jan 2011

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Giant Cell Tumor of Bone
Proteomics
Peroxiredoxins
Up-Regulation
Biomarkers
Neoplasm Metastasis
Ubiquitin
Lung
Allografts
HSP27 Heat-Shock Proteins
Giant Cell Tumors
Kaplan-Meier Estimate
Electrophoresis
Mass Spectrometry
Cell Cycle
Proteins
Coloring Agents
Down-Regulation
Apoptosis
Recurrence

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Identification of potential biomarkers for giant cell tumor of bone using comparative proteomics analysis. / Conti, Amalia; Rodriguez, Gemma Caballero; Chiechi, Antonella; Blazquez, Rosa Maria Dégano; Barbado, Victoria; Krènacs, Tibor; Novello, Chiara; Pazzaglia, Laura; Quattrini, Irene; Zanella, Licciana; Picci, Piero; De Alava, Enrique; Benassi, Maria Serena.

In: American Journal of Pathology, Vol. 178, No. 1, 01.2011, p. 88-97.

Research output: Contribution to journalArticle

Conti, A, Rodriguez, GC, Chiechi, A, Blazquez, RMD, Barbado, V, Krènacs, T, Novello, C, Pazzaglia, L, Quattrini, I, Zanella, L, Picci, P, De Alava, E & Benassi, MS 2011, 'Identification of potential biomarkers for giant cell tumor of bone using comparative proteomics analysis', American Journal of Pathology, vol. 178, no. 1, pp. 88-97. https://doi.org/10.1016/j.ajpath.2010.11.035
Conti, Amalia ; Rodriguez, Gemma Caballero ; Chiechi, Antonella ; Blazquez, Rosa Maria Dégano ; Barbado, Victoria ; Krènacs, Tibor ; Novello, Chiara ; Pazzaglia, Laura ; Quattrini, Irene ; Zanella, Licciana ; Picci, Piero ; De Alava, Enrique ; Benassi, Maria Serena. / Identification of potential biomarkers for giant cell tumor of bone using comparative proteomics analysis. In: American Journal of Pathology. 2011 ; Vol. 178, No. 1. pp. 88-97.
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