Gene signatures of progression and metastasis in renal cell cancer

Jon Jones, Hasan Otu, Dimitrios Spentzos, Shakirahmed Kolia, Mehmet Inan, Wolf D. Beecken, Christian Fellbaum, Xuesong Gu, Marie Joseph, Allan J. Pantuck, Dietger Jonas, Towia A. Libermann

Research output: Contribution to journalArticle

263 Citations (Scopus)

Abstract

Purpose: To address the progression, metastasis, and clinical heterogeneity of renal cell cancer (RCC). Experimental Design: Transcriptional profiling with oligonucleotide microarrays (22,283 genes) was done on 49 RCC tumors, 20 non-RCC renal tumors, and 23 normal kidney samples. Samples were clustered based on gene expression profiles and specific gene sets for each renal tumor type were identified. Gene expression was correlated to disease progression and a metastasis gene signature was derived. Results: Gene signatures were identified for each tumor type with 100% accuracy. Differentially expressed genes during early tumor formation and tumor progression to metastatic RCC were found. Subsets of these genes code for secreted proteins and membrane receptors and are both potential therapeutic or diagnostic targets. A gene pattern ("metastatic signature") derived from primary tumor was very accurate in classifying tumors with and without metastases at the time of surgery. A previously described "global" metastatic signature derived by another group from various non-RCC tumors was validated in RCC. Conclusion: Unlike previous studies, we describe highly accurate and externally validated gene signatures for RCC subtypes and other renal tumors. Interestingly, the gene expression of primary tumors provides us information about the metastatic status in the respective patients and has the potential, if prospectively validated, to enrich the armamentarium of diagnostic tests in RCC. We validated in RCC, for the first time, a previously described metastatic signature and further showed the feasibility of applying a gene signature across different microarray platforms. Transcriptional profiling allows a better appreciation of the molecular and clinical heterogeneity in RCC.

Original languageEnglish (US)
Pages (from-to)5730-5739
Number of pages10
JournalClinical Cancer Research
Volume11
Issue number16
DOIs
StatePublished - Aug 15 2005

Fingerprint

Renal Cell Carcinoma
Neoplasm Metastasis
Genes
Neoplasms
Kidney
Gene Expression
Oligonucleotide Array Sequence Analysis
Transcriptome
Routine Diagnostic Tests
Disease Progression
Membrane Proteins
Research Design

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Jones, J., Otu, H., Spentzos, D., Kolia, S., Inan, M., Beecken, W. D., ... Libermann, T. A. (2005). Gene signatures of progression and metastasis in renal cell cancer. Clinical Cancer Research, 11(16), 5730-5739. https://doi.org/10.1158/1078-0432.CCR-04-2225

Gene signatures of progression and metastasis in renal cell cancer. / Jones, Jon; Otu, Hasan; Spentzos, Dimitrios; Kolia, Shakirahmed; Inan, Mehmet; Beecken, Wolf D.; Fellbaum, Christian; Gu, Xuesong; Joseph, Marie; Pantuck, Allan J.; Jonas, Dietger; Libermann, Towia A.

In: Clinical Cancer Research, Vol. 11, No. 16, 15.08.2005, p. 5730-5739.

Research output: Contribution to journalArticle

Jones, J, Otu, H, Spentzos, D, Kolia, S, Inan, M, Beecken, WD, Fellbaum, C, Gu, X, Joseph, M, Pantuck, AJ, Jonas, D & Libermann, TA 2005, 'Gene signatures of progression and metastasis in renal cell cancer', Clinical Cancer Research, vol. 11, no. 16, pp. 5730-5739. https://doi.org/10.1158/1078-0432.CCR-04-2225
Jones, Jon ; Otu, Hasan ; Spentzos, Dimitrios ; Kolia, Shakirahmed ; Inan, Mehmet ; Beecken, Wolf D. ; Fellbaum, Christian ; Gu, Xuesong ; Joseph, Marie ; Pantuck, Allan J. ; Jonas, Dietger ; Libermann, Towia A. / Gene signatures of progression and metastasis in renal cell cancer. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 16. pp. 5730-5739.
@article{4d4a9d78107c46db81eaafc0f2ee0d32,
title = "Gene signatures of progression and metastasis in renal cell cancer",
abstract = "Purpose: To address the progression, metastasis, and clinical heterogeneity of renal cell cancer (RCC). Experimental Design: Transcriptional profiling with oligonucleotide microarrays (22,283 genes) was done on 49 RCC tumors, 20 non-RCC renal tumors, and 23 normal kidney samples. Samples were clustered based on gene expression profiles and specific gene sets for each renal tumor type were identified. Gene expression was correlated to disease progression and a metastasis gene signature was derived. Results: Gene signatures were identified for each tumor type with 100{\%} accuracy. Differentially expressed genes during early tumor formation and tumor progression to metastatic RCC were found. Subsets of these genes code for secreted proteins and membrane receptors and are both potential therapeutic or diagnostic targets. A gene pattern ({"}metastatic signature{"}) derived from primary tumor was very accurate in classifying tumors with and without metastases at the time of surgery. A previously described {"}global{"} metastatic signature derived by another group from various non-RCC tumors was validated in RCC. Conclusion: Unlike previous studies, we describe highly accurate and externally validated gene signatures for RCC subtypes and other renal tumors. Interestingly, the gene expression of primary tumors provides us information about the metastatic status in the respective patients and has the potential, if prospectively validated, to enrich the armamentarium of diagnostic tests in RCC. We validated in RCC, for the first time, a previously described metastatic signature and further showed the feasibility of applying a gene signature across different microarray platforms. Transcriptional profiling allows a better appreciation of the molecular and clinical heterogeneity in RCC.",
author = "Jon Jones and Hasan Otu and Dimitrios Spentzos and Shakirahmed Kolia and Mehmet Inan and Beecken, {Wolf D.} and Christian Fellbaum and Xuesong Gu and Marie Joseph and Pantuck, {Allan J.} and Dietger Jonas and Libermann, {Towia A.}",
year = "2005",
month = "8",
day = "15",
doi = "10.1158/1078-0432.CCR-04-2225",
language = "English (US)",
volume = "11",
pages = "5730--5739",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "16",

}

TY - JOUR

T1 - Gene signatures of progression and metastasis in renal cell cancer

AU - Jones, Jon

AU - Otu, Hasan

AU - Spentzos, Dimitrios

AU - Kolia, Shakirahmed

AU - Inan, Mehmet

AU - Beecken, Wolf D.

AU - Fellbaum, Christian

AU - Gu, Xuesong

AU - Joseph, Marie

AU - Pantuck, Allan J.

AU - Jonas, Dietger

AU - Libermann, Towia A.

PY - 2005/8/15

Y1 - 2005/8/15

N2 - Purpose: To address the progression, metastasis, and clinical heterogeneity of renal cell cancer (RCC). Experimental Design: Transcriptional profiling with oligonucleotide microarrays (22,283 genes) was done on 49 RCC tumors, 20 non-RCC renal tumors, and 23 normal kidney samples. Samples were clustered based on gene expression profiles and specific gene sets for each renal tumor type were identified. Gene expression was correlated to disease progression and a metastasis gene signature was derived. Results: Gene signatures were identified for each tumor type with 100% accuracy. Differentially expressed genes during early tumor formation and tumor progression to metastatic RCC were found. Subsets of these genes code for secreted proteins and membrane receptors and are both potential therapeutic or diagnostic targets. A gene pattern ("metastatic signature") derived from primary tumor was very accurate in classifying tumors with and without metastases at the time of surgery. A previously described "global" metastatic signature derived by another group from various non-RCC tumors was validated in RCC. Conclusion: Unlike previous studies, we describe highly accurate and externally validated gene signatures for RCC subtypes and other renal tumors. Interestingly, the gene expression of primary tumors provides us information about the metastatic status in the respective patients and has the potential, if prospectively validated, to enrich the armamentarium of diagnostic tests in RCC. We validated in RCC, for the first time, a previously described metastatic signature and further showed the feasibility of applying a gene signature across different microarray platforms. Transcriptional profiling allows a better appreciation of the molecular and clinical heterogeneity in RCC.

AB - Purpose: To address the progression, metastasis, and clinical heterogeneity of renal cell cancer (RCC). Experimental Design: Transcriptional profiling with oligonucleotide microarrays (22,283 genes) was done on 49 RCC tumors, 20 non-RCC renal tumors, and 23 normal kidney samples. Samples were clustered based on gene expression profiles and specific gene sets for each renal tumor type were identified. Gene expression was correlated to disease progression and a metastasis gene signature was derived. Results: Gene signatures were identified for each tumor type with 100% accuracy. Differentially expressed genes during early tumor formation and tumor progression to metastatic RCC were found. Subsets of these genes code for secreted proteins and membrane receptors and are both potential therapeutic or diagnostic targets. A gene pattern ("metastatic signature") derived from primary tumor was very accurate in classifying tumors with and without metastases at the time of surgery. A previously described "global" metastatic signature derived by another group from various non-RCC tumors was validated in RCC. Conclusion: Unlike previous studies, we describe highly accurate and externally validated gene signatures for RCC subtypes and other renal tumors. Interestingly, the gene expression of primary tumors provides us information about the metastatic status in the respective patients and has the potential, if prospectively validated, to enrich the armamentarium of diagnostic tests in RCC. We validated in RCC, for the first time, a previously described metastatic signature and further showed the feasibility of applying a gene signature across different microarray platforms. Transcriptional profiling allows a better appreciation of the molecular and clinical heterogeneity in RCC.

UR - http://www.scopus.com/inward/record.url?scp=23844524767&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=23844524767&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-04-2225

DO - 10.1158/1078-0432.CCR-04-2225

M3 - Article

C2 - 16115910

AN - SCOPUS:23844524767

VL - 11

SP - 5730

EP - 5739

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 16

ER -