Clin Exp Metastasis. 2014 Jan;31(1):111-34. doi: 10.1007/s10585-013-9612-7.
Appropriate use of multiple reliable molecular biomarkers in the right context will play a role in tailormade medicine of clear cell renal cell carcinoma (RCC) patients in the future. A total of 11,056 patients from 53 studies were included in this review. The article numbers of the each evidence levels, using the grading system defined by the Oxford Centre for Evidence-based Medicine, in 1b, 2a, 2b, and 3b were 5 (9%), 18 (34%), 29 (55%), and 1 (2%), respectively. The main goal of using biomarkers is to refine predictions of tumor progression, pharmacotherapy responsiveness, and cancer-specific and/or overall survival. Currently, carbonic anhydrase (CA9) and vascular endothelial growth factor (VEGF) in peripheral blood and p53 in tumor tissues are measured to predict metastasis, while VEGF-related proteins in peripheral blood are used to assess pharmacotherapy responsiveness with sunitinib. Furthermore, interleukin 8, osteopontin, hepatocyte growth factor, and tissue inhibitors of metalloproteinases-1 in peripheral blood enable assessment of responsiveness to pazopanib treatment. Other reliable molecular biomarkers include von Hippel–Lindau gene alteration, hypoxia-inducible factor-1a, CA9, and survivin in tumor tissues and VEGF in peripheral blood for predicting cancer-specific survival. In the future, studies should undergo external validation for developing tailored management of clear cell RCC with molecular biomarkers, since individual institutional studies lack the generalization and consistency required to maintain accuracy among different patient series.
在适当的背景下,适当使用多种可靠的分子生物标志物将在未来为透明细胞肾细胞癌(RCC)患者的个体化医学发挥作用。本综述共纳入了来自 53 项研究的 11056 名患者。根据牛津循证医学中心定义的分级系统,使用证据水平的文章数量分别为 1b(5%)、2a(34%)、2b(55%)和 3b(2%)。使用生物标志物的主要目的是改进对肿瘤进展、药物治疗反应性以及癌症特异性和/或总体生存率的预测。目前,外周血中的碳酸酐酶(CA9)和血管内皮生长因子(VEGF)以及肿瘤组织中的 p53 用于预测转移,而外周血中的 VEGF 相关蛋白用于评估舒尼替尼的药物治疗反应性。此外,外周血中的白细胞介素 8、骨桥蛋白、肝细胞生长因子和金属蛋白酶组织抑制剂-1 可用于评估对帕唑帕尼治疗的反应性。其他可靠的分子生物标志物包括肿瘤组织中的von Hippel-Lindau 基因改变、缺氧诱导因子-1a、CA9 和生存素以及外周血中的 VEGF,用于预测癌症特异性生存率。未来,应进行外部验证,以利用分子生物标志物对透明细胞 RCC 进行个体化管理,因为个体机构研究缺乏在不同患者系列中保持准确性所需的概括性和一致性。