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Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process

BACKGROUND: Prostate cancer is characterized by heterogeneity in the clinical course that often does not correlate with morphologic features of the tumor. Metastasis reflects the most adverse outcome of prostate cancer, and to date there are no reliable morphologic features or serum biomarkers that...

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Autores principales: Chandran, Uma R, Ma, Changqing, Dhir, Rajiv, Bisceglia, Michelle, Lyons-Weiler, Maureen, Liang, Wenjing, Michalopoulos, George, Becich, Michael, Monzon, Federico A
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1865555/
https://www.ncbi.nlm.nih.gov/pubmed/17430594
http://dx.doi.org/10.1186/1471-2407-7-64
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author Chandran, Uma R
Ma, Changqing
Dhir, Rajiv
Bisceglia, Michelle
Lyons-Weiler, Maureen
Liang, Wenjing
Michalopoulos, George
Becich, Michael
Monzon, Federico A
author_facet Chandran, Uma R
Ma, Changqing
Dhir, Rajiv
Bisceglia, Michelle
Lyons-Weiler, Maureen
Liang, Wenjing
Michalopoulos, George
Becich, Michael
Monzon, Federico A
author_sort Chandran, Uma R
collection PubMed
description BACKGROUND: Prostate cancer is characterized by heterogeneity in the clinical course that often does not correlate with morphologic features of the tumor. Metastasis reflects the most adverse outcome of prostate cancer, and to date there are no reliable morphologic features or serum biomarkers that can reliably predict which patients are at higher risk of developing metastatic disease. Understanding the differences in the biology of metastatic and organ confined primary tumors is essential for developing new prognostic markers and therapeutic targets. METHODS: Using Affymetrix oligonucleotide arrays, we analyzed gene expression profiles of 24 androgen-ablation resistant metastatic samples obtained from 4 patients and a previously published dataset of 64 primary prostate tumor samples. Differential gene expression was analyzed after removing potentially uninformative stromal genes, addressing the differences in cellular content between primary and metastatic tumors. RESULTS: The metastatic samples are highly heterogenous in expression; however, differential expression analysis shows that 415 genes are upregulated and 364 genes are downregulated at least 2 fold in every patient with metastasis. The expression profile of metastatic samples reveals changes in expression of a unique set of genes representing both the androgen ablation related pathways and other metastasis related gene networks such as cell adhesion, bone remodelling and cell cycle. The differentially expressed genes include metabolic enzymes, transcription factors such as Forkhead Box M1 (FoxM1) and cell adhesion molecules such as Osteopontin (SPP1). CONCLUSION: We hypothesize that these genes have a role in the biology of metastatic disease and that they represent potential therapeutic targets for prostate cancer.
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spelling pubmed-18655552007-05-05 Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process Chandran, Uma R Ma, Changqing Dhir, Rajiv Bisceglia, Michelle Lyons-Weiler, Maureen Liang, Wenjing Michalopoulos, George Becich, Michael Monzon, Federico A BMC Cancer Research Article BACKGROUND: Prostate cancer is characterized by heterogeneity in the clinical course that often does not correlate with morphologic features of the tumor. Metastasis reflects the most adverse outcome of prostate cancer, and to date there are no reliable morphologic features or serum biomarkers that can reliably predict which patients are at higher risk of developing metastatic disease. Understanding the differences in the biology of metastatic and organ confined primary tumors is essential for developing new prognostic markers and therapeutic targets. METHODS: Using Affymetrix oligonucleotide arrays, we analyzed gene expression profiles of 24 androgen-ablation resistant metastatic samples obtained from 4 patients and a previously published dataset of 64 primary prostate tumor samples. Differential gene expression was analyzed after removing potentially uninformative stromal genes, addressing the differences in cellular content between primary and metastatic tumors. RESULTS: The metastatic samples are highly heterogenous in expression; however, differential expression analysis shows that 415 genes are upregulated and 364 genes are downregulated at least 2 fold in every patient with metastasis. The expression profile of metastatic samples reveals changes in expression of a unique set of genes representing both the androgen ablation related pathways and other metastasis related gene networks such as cell adhesion, bone remodelling and cell cycle. The differentially expressed genes include metabolic enzymes, transcription factors such as Forkhead Box M1 (FoxM1) and cell adhesion molecules such as Osteopontin (SPP1). CONCLUSION: We hypothesize that these genes have a role in the biology of metastatic disease and that they represent potential therapeutic targets for prostate cancer. BioMed Central 2007-04-12 /pmc/articles/PMC1865555/ /pubmed/17430594 http://dx.doi.org/10.1186/1471-2407-7-64 Text en Copyright © 2007 Chandran et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Chandran, Uma R
Ma, Changqing
Dhir, Rajiv
Bisceglia, Michelle
Lyons-Weiler, Maureen
Liang, Wenjing
Michalopoulos, George
Becich, Michael
Monzon, Federico A
Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process
title Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process
title_full Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process
title_fullStr Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process
title_full_unstemmed Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process
title_short Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process
title_sort gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1865555/
https://www.ncbi.nlm.nih.gov/pubmed/17430594
http://dx.doi.org/10.1186/1471-2407-7-64
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