Deregulation of energetic metabolism in the clear cell renal cell carcinoma: A multiple pathway analysis based on microarray profiling

Clear cell renal cell carcinoma (ccRCC) is the most frequent type of kidney cancer. In order to better understand the biology of ccRCC, we accomplished the gene profiling of fresh tissue specimens from 11 patients with the renal tumors (9 ccRCCs, 1 oncocytoma and 1 renal B-lymphoma), in which the tumor-related data were compared to the paired healthy kidney tissues from the same patients.

All ccRCCs exhibited a considerably elevated transcription of the gene coding for carbonic anhydrase IX (CAIX). Moreover, the ccRCC tumors consistently displayed increased expression of genes encoding the glycolytic pathway enzymes, e.g. hexokinase II (HK2) and lactate dehydrogenase A (LDHA) and a decreased expression of genes for the mitochondrial electron transport chain components, indicating an overall reprogramming of the energetic metabolism in this tumor type.

This appears to be accompanied by altered expression of the genes of the pH regulating machinery, including ion and lactate transporters. Immunohistochemical staining of tumor tissue sections confirmed the increased expression of CAIX, HK2 and LDHA in ccRCC, validating the microarray data and supporting their potential as the energetic metabolism-related biomarkers of the ccRCC.

Int J Oncol. 2015 Jul;47(1):287-95. doi: 10.3892/ijo.2015.3014. Epub 2015 May 19.

Soltysova A1, Breza J2, Takacova M3, Feruszova J1, Hudecova S1, Novotna B4, Rozborilova E5, Pastorekova S3, Kadasi L1, Krizanova O1.

1 Center for Molecular Medicine, Slovak Academy of Sciences, Bratislava, Slovakia.
2 Department of Urology, University Hospital, Bratislava, Slovakia.
3 Institute of Virology, Slovak Academy of Sciences, Bratislava, Slovakia.
4 Department of Neonatology and Pediatric Intensive Care, University Clinic Carl Gustav Carus, Dresden, Germany.
5 Clinic of Pneumology and Pthisiology, Jessenius Medical Faculty, Martin, Slovakia.