Department of Urology, Eberhard Karls University, Hoppe-Seyler- Strasse 3, 72076, Tuebingen, Germany.
Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.
J Cancer Res Clin Oncol. 2019 Jul;145(7):1835-1843. doi: 10.1007/s00432-019-02914-2. Epub 2019 Apr 22.
Based on the observation of beneficial effects on cancer metabolism, microenvironment, or VEGF-signaling, several non-anticancer drugs have been discussed as useful in renal cell carcinoma (RCC). In the present study, we investigated the prognostic impact of concomitant medication in RCC and correlated comedication with cell-cycle and proliferation activity in corresponding surgical specimen.
A total of 388 patients who underwent surgery for localized RCC were included. The individual medication was evaluated according to substance classes. Tissue microarrays from corresponding tumor specimen were immunohistochemically (IHC) stained for Cyclin D1 and Ki67 and semi-quantitatively evaluated. Uni- and multivariate analyses were used to compare survival outcomes. For the comparison of IHC expression according to medication subgroups, Kruskal-Wallis analysis was performed.
Median follow-up was 57.93 months (95% CI 53.27-69.43) and median OS accounted for 181.12 months (129.72-237.17). Univariate analysis identified pathological standard variables (T-stage > T2, Grading > G2, L1, N1, M1, sarcomatoid subtype, necrosis) as significant determinants of OS. Moreover, statin use (p = 0.009) and sartan use (p = 0.032) were significantly associated with improved OS. Multivariate analysis identified M1-stage (p < 0.001), statin and sartan use (p = 0.003 and p = 0.033, respectively) as independent prognosticators of survival. Expression of Ki67 was significantly reduced in patients with statin use (p = 0.013), while Cyclin D1 expression showed no correlation with comedication.
Concomitant intake of statins and sartans identifies as an independent predictor of OS in RCC, and reduced Ki67 expression was significantly associated with statin use. Further evaluation of drug repurposing approaches with these substances in RCC appear warranted.
基于对癌症代谢、微环境或 VEGF 信号的有益观察，几种非抗癌药物已被讨论为对肾细胞癌（RCC）有用。在本研究中，我们研究了 RCC 中合并用药的预后影响，并将合并用药与相应手术标本中的细胞周期和增殖活性相关联。
共纳入 388 例接受局部 RCC 手术的患者。根据物质类别评估个体用药。相应肿瘤标本的组织微阵列通过免疫组化（IHC）染色 Cyclin D1 和 Ki67，并进行半定量评估。采用单因素和多因素分析比较生存结果。为了比较根据药物亚组的 IHC 表达，进行了 Kruskal-Wallis 分析。
中位随访时间为 57.93 个月（95%CI 53.27-69.43），中位 OS 为 181.12 个月（129.72-237.17）。单因素分析确定了病理标准变量（T 期> T2、分级> G2、L1、N1、M1、肉瘤样亚型、坏死）是 OS 的显著决定因素。此外，他汀类药物使用（p=0.009）和沙坦类药物使用（p=0.032）与 OS 改善显著相关。多因素分析确定 M1 期（p<0.001）、他汀类药物和沙坦类药物使用（p=0.003 和 p=0.033）是生存的独立预后因素。他汀类药物使用者的 Ki67 表达显著降低（p=0.013），而 Cyclin D1 表达与合并用药无相关性。
他汀类药物和沙坦类药物的合并使用是 RCC 中 OS 的独立预测因子，Ki67 表达的降低与他汀类药物的使用显著相关。进一步评估这些物质在 RCC 中的药物再利用方法似乎是合理的。
