State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Biochem Biophys Res Commun. 2012 Oct 5;426(4):636-42. doi: 10.1016/j.bbrc.2012.08.146. Epub 2012 Sep 11.
ZBP-89, a Krüppel-type zinc-finger transcription factor, is found to participate in tumor development, invasion and metastasis. However, the expression status of ZBP-89 in clear cell renal cell carcinoma (CCRCC) remains elusive. Using quantitative real-time-PCR and Western Blot, we found that, in fresh cancer tissues, ZBP-89 was remarkably decreased in 79.2% (19/24) and 83.3% (5/6) of CCRCC at mRNA and protein level, respectively. Immunohistochemistry also revealed a significant decline of ZBP-89 expression in CCRCC, showing that low expression of ZBP-89 was present in 73.9% (105/142) of tumorous tissues but in 48.1% (52/108) of the corresponding adjacent kidney tissues. Furthermore, ZBP-89 expression in CCRCC was significantly correlated with several clinicopathological features, including TNM stage (P=0.005) and distal metastasis (P=0.001). Further study confirmed that ZBP-89 expression was markedly higher in metastatic CCRCC than that in non-metastatic tissue (P=0.002). In addition, CCRCC patients with low ZBP-89 expression survived longer than those with high ZBP-89 expression, as indicated by the result of univariate analysis (P<0.0001). More importantly, multivariate analysis revealed that ZBP-89 was an independent predictor of overall survival (HR, 2.871; 95% CI, 1.409-5.853; P=0.004). Collectively, our study provides vigorous evidence that ZBP-89 was significantly downregulated in CCRCC and could be served as a promising biomarker for prediction of distal metastasis and prognosis of patient with CCRCC.
ZBP-89 是一种 Kruppel 型锌指转录因子，被发现参与肿瘤的发生、侵袭和转移。然而，ZBP-89 在透明细胞肾细胞癌（ccRCC）中的表达状态仍不清楚。通过定量实时-PCR 和 Western blot，我们发现，在新鲜的癌组织中，ZBP-89 在 mRNA 和蛋白质水平上分别在 79.2%（24/24）和 83.3%（6/6）的 ccRCC 中显著降低。免疫组织化学也显示 ZBP-89 在 ccRCC 中的表达显著下降，表明低表达 ZBP-89 存在于 73.9%（105/142）的肿瘤组织中，但存在于 48.1%（52/108）的相应相邻肾组织中。此外，ZBP-89 在 ccRCC 中的表达与多种临床病理特征显著相关，包括 TNM 分期（P=0.005）和远处转移（P=0.001）。进一步的研究证实，ZBP-89 在转移性 ccRCC 中的表达明显高于非转移性组织（P=0.002）。此外，根据单因素分析的结果（P<0.0001），ZBP-89 低表达的 ccRCC 患者的生存时间明显长于 ZBP-89 高表达的患者。更重要的是，多因素分析显示 ZBP-89 是 ccRCC 患者总生存的独立预测因子（HR，2.871；95%CI，1.409-5.853；P=0.004）。综上所述，我们的研究提供了有力的证据，表明 ZBP-89 在 ccRCC 中显著下调，可作为预测 ccRCC 患者远处转移和预后的有前途的生物标志物。
