Gene signatures of progression and metastasis in renal cell cancer.
OBJECTIVE
To address the progression, metastasis, and clinical heterogeneity of renal cell cancer (RCC).


METHODS
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.


CONCLUSIONS
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.
Jones
Jon
J
Beth Israel Deaconess Medical Center Genomics Center and Dana-Farber/Harvard Cancer Center Proteomics Core, Boston, Massachusetts 02115, USA.
Otu
Hasan
H
Spentzos
Dimitrios
D
Kolia
Shakirahmed
S
Inan
Mehmet
M
Beecken
Wolf D
WD
Fellbaum
Christian
C
Gu
Xuesong
X
Joseph
Marie
M
Pantuck
Allan J
AJ
Jonas
Dietger
D
Libermann
Towia A
TA
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D016000:Cluster Analysis; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D015854:Up-Regulation / Q000235:genetics