Soltysova Andrea, Breza Jan, Takacova Martina, Feruszova Jana, Hudecova Sona, Novotna Barbora, Rozborilova Eva, Pastorekova Silvia, Kadasi Ludevit, Krizanova Olga
Center for Molecular Medicine, Slovak Academy of Sciences, Bratislava, Slovakia.
Department of Urology, University Hospital, Bratislava, Slovakia.
Int J Oncol. 2015 Jul;47(1):287-95. doi: 10.3892/ijo.2015.3014. Epub 2015 May 19.
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.
透明细胞肾细胞癌（ccRCC）是最常见的肾癌类型。为了更好地了解ccRCC的生物学特性，我们对11例肾肿瘤患者（9例ccRCC、1例嗜酸细胞瘤和1例肾B淋巴瘤）的新鲜组织标本进行了基因谱分析，并将肿瘤相关数据与同一患者配对的健康肾组织进行了比较。所有ccRCC均表现出编码碳酸酐酶IX（CAIX）的基因转录显著升高。此外，ccRCC肿瘤始终显示编码糖酵解途径酶的基因表达增加，如己糖激酶II（HK2）和乳酸脱氢酶A（LDHA），而线粒体电子传递链成分的基因表达降低，这表明该肿瘤类型的能量代谢总体上发生了重编程。这似乎伴随着pH调节机制相关基因的表达改变，包括离子和乳酸转运体。肿瘤组织切片的免疫组织化学染色证实了ccRCC中CAIX、HK2和LDHA的表达增加，验证了微阵列数据，并支持它们作为ccRCC能量代谢相关生物标志物的潜力。
