Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Institute of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Department of Pathogenic Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan 430030, China.
Exp Cell Res. 2019 Mar 15;376(2):181-191. doi: 10.1016/j.yexcr.2019.02.001. Epub 2019 Feb 4.
Renal cell carcinomas are a group of most common renal malignancies whose clinical intervention is complicated by the lack of early diagnosis and reliable prognosis biomarkers, insensitive radiotherapy and chemotherapy and expensive molecular-targeted drugs. Transcriptional coactivator TAZ has been implicated in the formation and development of various malignancies. However, the biological characteristics and function of TAZ in renal cell carcinoma are still unclear. We attempted to evaluate the potential of TAZ as a promising diagnostic and prognostic molecular marker for renal cell carcinoma. In our study, we confirmed that TAZ was frequently elevated in renal cancer tissues and cells, consistent with the results of the publicly available cancer database. Moreover, elevated TAZ expression was positively correlated with poor overall survival time, high Fuhrman grade and distant metastasis. Our receiver operating characteristic curves analysis showed that high TAZ expression could distinguish renal cancer patients from normal persons (p < 0.0001). Kaplan-Meier curves demonstrated that high TAZ expression predicted poor overall survival (p < 0.0001). Multivariate regression analysis indicated that TAZ expression could be an independent prognostic factor (p = 0.002) in patients with renal cancer. Finally, the functional roles of TAZ knockdown were examined in renal cancer cell lines and nude mice subcutaneous tumor models. In conclusion, our results suggest that TAZ may serve as a promising diagnostic and prognostic molecular marker for patients with renal cancer. Moreover, TAZ may represent a novel clinical therapeutic target.
肾细胞癌是一组最常见的肾恶性肿瘤，由于缺乏早期诊断和可靠的预后生物标志物、放疗和化疗不敏感以及昂贵的分子靶向药物，其临床干预变得复杂。转录共激活因子 TAZ 与各种恶性肿瘤的形成和发展有关。然而，TAZ 在肾细胞癌中的生物学特征和功能仍不清楚。我们试图评估 TAZ 作为肾细胞癌有前途的诊断和预后分子标志物的潜力。在我们的研究中，我们证实 TAZ 在肾癌组织和细胞中经常升高，与公开可用的癌症数据库的结果一致。此外，升高的 TAZ 表达与总生存期不良、Fuhrman 分级高和远处转移呈正相关。我们的受试者工作特征曲线分析表明，高 TAZ 表达可以区分肾癌患者和正常人（p<0.0001）。Kaplan-Meier 曲线表明，高 TAZ 表达预示着总生存期不良（p<0.0001）。多变量回归分析表明，TAZ 表达可以作为肾癌患者的独立预后因素（p=0.002）。最后，在肾癌细胞系和裸鼠皮下肿瘤模型中检查了 TAZ 敲低的功能作用。总之，我们的结果表明，TAZ 可能是肾细胞癌患者有前途的诊断和预后分子标志物。此外，TAZ 可能代表一种新的临床治疗靶点。
