Receptor Activator of NF-kB (RANK) Expression in Primary Tumors Associates with Bone Metastasis Occurrence in Breast Cancer Patients

Antonio Russo, Cinzia Caroti, Sara Galluzzo, Raffaele Addeo, Bruno Vincenzi, Giuseppe Tonini, Daniele Santini, Cinzia Ortega, Francesco Pantano, Nicla La Verde, Camillo Porta, Alessandro Ruggiero, Grazia Armento, Isabelle Treilleux, Andrea Onetti Muda, Philippe Clezardin, Giuseppe Perrone, Laura Gaeta, Gaia Schiavon

Risultato della ricerca: Article

112 Citazioni (Scopus)

Abstract

Background: Receptor activator of NFkB (RANK), its ligand (RANKL) and the decoy receptor of RANKL (osteoprotegerin, OPG) play a pivotal role in bone remodeling by regulating osteoclasts formation and activity. RANKL stimulates migration of RANK-expressing tumor cells in vitro, conversely inhibited by OPG. Materials and Methods: We examined mRNA expression levels of RANKL/RANK/OPG in a publicly available microarray dataset of 295 primary breast cancer patients. We next analyzed RANK expression by immunohistochemistry in an independent series of 93 primary breast cancer specimens and investigated a possible association with clinicopathological parameters, bone recurrence and survival. Results: Microarray analysis showed that lower RANK and high OPG mRNA levels correlate with longer overall survival (P = 0.0078 and 0.0335, respectively) and disease-free survival (P = 0.059 and 0.0402, respectively). Immunohistochemical analysis of RANK showed a positive correlation with the development of bone metastases (P = 0.023) and a shorter skeletal disease-free survival (SDFS, P = 0.037). Specifically, univariate analysis of survival showed that "RANK-negative" and "RANK-positive" patients had a SDFS of 105.7 months (95% CI: 73.9-124.4) and 58.9 months (95% CI: 34.7-68.5), respectively. RANK protein expression was also associated with accelerated bone metastasis formation in a multivariate analysis (P = 0.029). Conclusions: This is the first demonstration of the role of RANK expression in primary tumors as a predictive marker of bone metastasis occurrence and SDFS in a large population of breast cancer patients.
Lingua originaleEnglish
pagine (da-a)-
Numero di pagine0
RivistaPLoS One
Volume6
Stato di pubblicazionePublished - 2011

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transcription factor NF-kappa B
NF-kappa B
metastasis
breast neoplasms
Tumors
Bone
bones
Breast Neoplasms
Neoplasm Metastasis
Bone and Bones
receptors
neoplasms
Osteoprotegerin
RANK Ligand
Neoplasms
Microarrays
Disease-Free Survival
Messenger RNA
Survival
Bone Remodeling

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cita questo

Russo, A., Caroti, C., Galluzzo, S., Addeo, R., Vincenzi, B., Tonini, G., ... Schiavon, G. (2011). Receptor Activator of NF-kB (RANK) Expression in Primary Tumors Associates with Bone Metastasis Occurrence in Breast Cancer Patients. PLoS One, 6, -.

Receptor Activator of NF-kB (RANK) Expression in Primary Tumors Associates with Bone Metastasis Occurrence in Breast Cancer Patients. / Russo, Antonio; Caroti, Cinzia; Galluzzo, Sara; Addeo, Raffaele; Vincenzi, Bruno; Tonini, Giuseppe; Santini, Daniele; Ortega, Cinzia; Pantano, Francesco; La Verde, Nicla; Porta, Camillo; Ruggiero, Alessandro; Armento, Grazia; Treilleux, Isabelle; Muda, Andrea Onetti; Clezardin, Philippe; Perrone, Giuseppe; Gaeta, Laura; Schiavon, Gaia.

In: PLoS One, Vol. 6, 2011, pag. -.

Risultato della ricerca: Article

Russo, A, Caroti, C, Galluzzo, S, Addeo, R, Vincenzi, B, Tonini, G, Santini, D, Ortega, C, Pantano, F, La Verde, N, Porta, C, Ruggiero, A, Armento, G, Treilleux, I, Muda, AO, Clezardin, P, Perrone, G, Gaeta, L & Schiavon, G 2011, 'Receptor Activator of NF-kB (RANK) Expression in Primary Tumors Associates with Bone Metastasis Occurrence in Breast Cancer Patients', PLoS One, vol. 6, pagg. -.
Russo, Antonio ; Caroti, Cinzia ; Galluzzo, Sara ; Addeo, Raffaele ; Vincenzi, Bruno ; Tonini, Giuseppe ; Santini, Daniele ; Ortega, Cinzia ; Pantano, Francesco ; La Verde, Nicla ; Porta, Camillo ; Ruggiero, Alessandro ; Armento, Grazia ; Treilleux, Isabelle ; Muda, Andrea Onetti ; Clezardin, Philippe ; Perrone, Giuseppe ; Gaeta, Laura ; Schiavon, Gaia. / Receptor Activator of NF-kB (RANK) Expression in Primary Tumors Associates with Bone Metastasis Occurrence in Breast Cancer Patients. In: PLoS One. 2011 ; Vol. 6. pagg. -.
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abstract = "Background: Receptor activator of NFkB (RANK), its ligand (RANKL) and the decoy receptor of RANKL (osteoprotegerin, OPG) play a pivotal role in bone remodeling by regulating osteoclasts formation and activity. RANKL stimulates migration of RANK-expressing tumor cells in vitro, conversely inhibited by OPG. Materials and Methods: We examined mRNA expression levels of RANKL/RANK/OPG in a publicly available microarray dataset of 295 primary breast cancer patients. We next analyzed RANK expression by immunohistochemistry in an independent series of 93 primary breast cancer specimens and investigated a possible association with clinicopathological parameters, bone recurrence and survival. Results: Microarray analysis showed that lower RANK and high OPG mRNA levels correlate with longer overall survival (P = 0.0078 and 0.0335, respectively) and disease-free survival (P = 0.059 and 0.0402, respectively). Immunohistochemical analysis of RANK showed a positive correlation with the development of bone metastases (P = 0.023) and a shorter skeletal disease-free survival (SDFS, P = 0.037). Specifically, univariate analysis of survival showed that {"}RANK-negative{"} and {"}RANK-positive{"} patients had a SDFS of 105.7 months (95{\%} CI: 73.9-124.4) and 58.9 months (95{\%} CI: 34.7-68.5), respectively. RANK protein expression was also associated with accelerated bone metastasis formation in a multivariate analysis (P = 0.029). Conclusions: This is the first demonstration of the role of RANK expression in primary tumors as a predictive marker of bone metastasis occurrence and SDFS in a large population of breast cancer patients.",
author = "Antonio Russo and Cinzia Caroti and Sara Galluzzo and Raffaele Addeo and Bruno Vincenzi and Giuseppe Tonini and Daniele Santini and Cinzia Ortega and Francesco Pantano and {La Verde}, Nicla and Camillo Porta and Alessandro Ruggiero and Grazia Armento and Isabelle Treilleux and Muda, {Andrea Onetti} and Philippe Clezardin and Giuseppe Perrone and Laura Gaeta and Gaia Schiavon",
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TY - JOUR

T1 - Receptor Activator of NF-kB (RANK) Expression in Primary Tumors Associates with Bone Metastasis Occurrence in Breast Cancer Patients

AU - Russo, Antonio

AU - Caroti, Cinzia

AU - Galluzzo, Sara

AU - Addeo, Raffaele

AU - Vincenzi, Bruno

AU - Tonini, Giuseppe

AU - Santini, Daniele

AU - Ortega, Cinzia

AU - Pantano, Francesco

AU - La Verde, Nicla

AU - Porta, Camillo

AU - Ruggiero, Alessandro

AU - Armento, Grazia

AU - Treilleux, Isabelle

AU - Muda, Andrea Onetti

AU - Clezardin, Philippe

AU - Perrone, Giuseppe

AU - Gaeta, Laura

AU - Schiavon, Gaia

PY - 2011

Y1 - 2011

N2 - Background: Receptor activator of NFkB (RANK), its ligand (RANKL) and the decoy receptor of RANKL (osteoprotegerin, OPG) play a pivotal role in bone remodeling by regulating osteoclasts formation and activity. RANKL stimulates migration of RANK-expressing tumor cells in vitro, conversely inhibited by OPG. Materials and Methods: We examined mRNA expression levels of RANKL/RANK/OPG in a publicly available microarray dataset of 295 primary breast cancer patients. We next analyzed RANK expression by immunohistochemistry in an independent series of 93 primary breast cancer specimens and investigated a possible association with clinicopathological parameters, bone recurrence and survival. Results: Microarray analysis showed that lower RANK and high OPG mRNA levels correlate with longer overall survival (P = 0.0078 and 0.0335, respectively) and disease-free survival (P = 0.059 and 0.0402, respectively). Immunohistochemical analysis of RANK showed a positive correlation with the development of bone metastases (P = 0.023) and a shorter skeletal disease-free survival (SDFS, P = 0.037). Specifically, univariate analysis of survival showed that "RANK-negative" and "RANK-positive" patients had a SDFS of 105.7 months (95% CI: 73.9-124.4) and 58.9 months (95% CI: 34.7-68.5), respectively. RANK protein expression was also associated with accelerated bone metastasis formation in a multivariate analysis (P = 0.029). Conclusions: This is the first demonstration of the role of RANK expression in primary tumors as a predictive marker of bone metastasis occurrence and SDFS in a large population of breast cancer patients.

AB - Background: Receptor activator of NFkB (RANK), its ligand (RANKL) and the decoy receptor of RANKL (osteoprotegerin, OPG) play a pivotal role in bone remodeling by regulating osteoclasts formation and activity. RANKL stimulates migration of RANK-expressing tumor cells in vitro, conversely inhibited by OPG. Materials and Methods: We examined mRNA expression levels of RANKL/RANK/OPG in a publicly available microarray dataset of 295 primary breast cancer patients. We next analyzed RANK expression by immunohistochemistry in an independent series of 93 primary breast cancer specimens and investigated a possible association with clinicopathological parameters, bone recurrence and survival. Results: Microarray analysis showed that lower RANK and high OPG mRNA levels correlate with longer overall survival (P = 0.0078 and 0.0335, respectively) and disease-free survival (P = 0.059 and 0.0402, respectively). Immunohistochemical analysis of RANK showed a positive correlation with the development of bone metastases (P = 0.023) and a shorter skeletal disease-free survival (SDFS, P = 0.037). Specifically, univariate analysis of survival showed that "RANK-negative" and "RANK-positive" patients had a SDFS of 105.7 months (95% CI: 73.9-124.4) and 58.9 months (95% CI: 34.7-68.5), respectively. RANK protein expression was also associated with accelerated bone metastasis formation in a multivariate analysis (P = 0.029). Conclusions: This is the first demonstration of the role of RANK expression in primary tumors as a predictive marker of bone metastasis occurrence and SDFS in a large population of breast cancer patients.

UR - http://hdl.handle.net/10447/75002

UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084800/

M3 - Article

VL - 6

SP - -

JO - PLoS One

JF - PLoS One

SN - 1932-6203

ER -