Department of Urology, Hannover Medical School, Germany.
Biomark Med. 2011 Apr;5(2):219-25. doi: 10.2217/bmm.11.12.
BACKGROUND & AIM: Caveolae play a significant role in disease phenotypes, such as cancer, diabetes, bladder dysfunction and muscular dystrophy. The aim of this study was to elucidate the expression of caveolin (CAV)1 in the development of renal cell cancer (RCC) and to determine a possible prognostic relevance for optimal clinical management.
MATERIAL & METHODS: 109 RCC and 81 corresponding normal tissue specimens from the same kidney were collected from patients undergoing surgery for renal tumors and subjected to total RNA extraction. Quantification of CAV1 mRNA expression was performed using real-time reverse transcription PCR with three endogenous controls for renal proximal tubular epithelial cells and the ΔΔCt method for calculation of relative quantities. Expression levels were correlated to clinical variables.
Tissue-specific mean CAV1 expression was significantly increased in RCC compared with normal renal tissue (p = 0.0003; paired Wilcoxon rank sum test). CAV1 expression was increased 1.9-fold in clear cell RCC compared with papillary RCC (p = 1.48 × 10(-7); unpaired Wilcoxon rank sum test). Patients with advanced disease had higher CAV1 expression when compared with organ-confined disease (p = 0.019; unpaired Wilcoxon rank sum test). Moreover, mean tissue-specific CAV1 expression was increased in patients with distant metastasis at the time of diagnosis compared with patients without metastasis (p = 0.0058; unpaired Wilcoxon rank sum test).
To our knowledge, this is the first study to show that CAV1 mRNA expression, using quantitative real-time PCR, is significantly higher in RCC compared with normal renal tissue and increases with tumor stage. CAV1 mRNA expression might serve as a candidate biomarker for objective prognosis indicating RCC aggressiveness. Our data encourage further investigations to determine the role of CAV1 in RCC.
小窝(caveolae)在疾病表型中发挥重要作用,例如癌症、糖尿病、膀胱功能障碍和肌肉营养不良。本研究旨在阐明小窝蛋白(CAV)1 在肾细胞癌(RCC)发展中的表达,并确定其对最佳临床管理的可能预后相关性。
从因肾脏肿瘤接受手术的患者中收集了 109 例 RCC 和 81 例相应的正常组织标本,进行总 RNA 提取。使用实时逆转录 PCR 结合三种肾近端管状上皮细胞内源性对照物和 ΔΔCt 方法计算相对数量,对 CAV1 mRNA 表达进行定量。将表达水平与临床变量相关联。
与正常肾组织相比,组织特异性 CAV1 表达在 RCC 中显著增加(p = 0.0003;配对 Wilcoxon 秩和检验)。与乳头状 RCC 相比,透明细胞 RCC 中 CAV1 表达增加了 1.9 倍(p = 1.48×10(-7);非配对 Wilcoxon 秩和检验)。与局限于器官的疾病相比,晚期疾病患者的 CAV1 表达更高(p = 0.019;非配对 Wilcoxon 秩和检验)。此外,与无转移的患者相比,诊断时远处转移的患者的组织特异性 CAV1 表达平均值更高(p = 0.0058;非配对 Wilcoxon 秩和检验)。
据我们所知,这是第一项使用定量实时 PCR 显示 CAV1 mRNA 表达在 RCC 中明显高于正常肾组织且随肿瘤分期而增加的研究。CAV1 mRNA 表达可能作为客观预后的候选生物标志物,表明 RCC 的侵袭性。我们的数据鼓励进一步研究以确定 CAV1 在 RCC 中的作用。