Identification of stanniocalcin 2 as prognostic marker in renal cell carcinoma.
BACKGROUND
For an individualized therapy in renal cell carcinoma (RCC), there is a clear need for novel prognostic biomarkers to ensure adequate risk stratification and help with the choice of therapy options.


OBJECTIVE
To identify new secreted biomarkers for diagnosis and estimation of prognosis in RCC.


METHODS
A meta-analysis of published microarray data was performed. Stanniocalcin 2 (STC2), a glycoprotein hormone that is involved in regulatory effects on calcium and phosphate transport in the kidney, was found overexpressed in tumors and hence analyzed in detail. Kidney tissue samples derived from 108 patients with RCC undergoing radical nephrectomy between July 2003 and January 2006 were used to validate and estimate the potential of STC2 as a biomarker for RCC.


METHODS
STC2, found upregulated in clear cell RCC, was analyzed in detail using real-time reverse transcription-polymerase chain reaction (RT-PCR), western blotting, and immunohistochemistry. Furthermore, STC2 protein expression determined on a tissue microarray was correlated to clinical pathologic parameters, including patient survival.


CONCLUSIONS
STC2 was upregulated at the mRNA and protein levels in RCC. In normal renal tissue, STC2 expression was limited to distal tubuli and glomeruli, whereas in tumor a strong cytoplasmic and also membranous staining was detected. STC2 expression was found in clear cell, chromophobe, and papillary RCC. Strong cytoplasmic STC2 expression was significantly associated with shorter patient survival in Kaplan-Meier analyses. In the group of patients without metastases, cytoplasmic STC2 expression was also found as a significant independent risk factor in multivariate analysis. A limitation of the study is the small number of patients.


CONCLUSIONS
Increased cytoplasmic STC2 expression correlated with conventional indicators of aggressiveness of RCC and shorter overall patient survival times. STC2 could become an adjunct tissue biomarker that may be useful in the postoperative risk stratification of RCC patients.
Meyer
Hellmuth-A
HA
Department of Urology, Charité-University Medicine Berlin, Campus Charité Mitte, Berlin, Germany. hellmuth.meyer@charite.de
Tölle
Angelika
A
Jung
Monika
M
Fritzsche
Florian R
FR
Haendler
Bernard
B
Kristiansen
Ilka
I
Gaspert
Ariana
A
Johannsen
Manfred
M
Jung
Klaus
K
Kristiansen
Glen
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D002292:Carcinoma, Renal Cell / Q000737:chemistry* / Q000378:metabolism / Q000401:mortality; D005260:Female; D006023:Glycoproteins / Q000032:analysis* / Q000096:biosynthesis; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis* / Q000096:biosynthesis; D007680:Kidney Neoplasms / Q000737:chemistry* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate
D015415:Biomarkers; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C114997:STC2 protein, human