Putative Biomarker Genes for Grading Clear Cell Renal Cell Carcinoma

Abstract

Objective: The initial objective of this renal cancer study was to identify gene sets in clear cell renal cell carcinoma (ccRCC) to support grading of ccRCC histopathology. Materials and Methods: Preselected ccRCC tumor tissues of grade 1 (G1, n = 14) and grade 3 (G3, n = 15) as well es 14 normal kidney tissues thereof were subjected to microarray expression analysis using Human Genome U133 Plus 2.0 Array. Event ratio scoring, hierarchical clustering and principal component analysis were used to determine gene sets that distinguish expression profiles from normal kidney tissue, G1 and G3 tumor tissues. Results: An initial set of 73 genes provided seven gene subclusters (SC01 to SC07) that distinguish RNA expression profiles from G1, G3 tumor and normal kidney tissues. A ranked list of 24 genes was determined that separated G1 from G3 tumors in high concordance with histopathological grading confirmed by immunohistochemical analysis of ceruloplasmin protein expression. Conclusion: A final set of 24 genes has been determined awaiting further validation on the RNA as well as on the protein level by studying an additional cohort of ccRCC patients. A reliable separation of G1 and G3 tumor grades will be instrumental to foster and direct the administration of upcoming targeted therapeutics of ccRCC tumors in a more predictive and reliable manner.

Microarrays and Renal Cell Cancer Biomarkers

“…Critical biologic processes were suggested for ccRCC (angiogenic and immune response), oxidative phosphorylation for chRCC, and serine protease inhibitors as well as extracellular matrix products for pRCC (Schuetz et al 2005). Other global gene expression patterns involving different candidates to further subclassify ccRCC did not only show subtype specificity, they were moreover able to separate tumor grades, thus confirming the histopathologic grading system on the molecular level (Skubitz et al 2006;Maruschke et al 2011).…”

Copy Number Alterations with Prognostic Potential in Clear Cell Renal Cell Carcinoma

“…We formerly reported our findings in gene expression profiling on the mRNA and cytogenetic level of ccRCC with different degrees of differentiation and suggested potential prognostic biomarkers identified by different biostatistical methods [9][10][11].…”

Expression profiling of metastatic renal cell carcinoma using gene set enrichment analysis

“…Subsequent validation studies must be carried out using new samples and additional methods (quantitative reverse transcription polymerase chain reaction, western blot etc.). Several studies published a panel of promising biomarkers . All potential markers will have to be validated in large‐cohort studies before they can be considered for clinical routine application.…”