Ma Xin, Wang Lei, Li Hongzhao, Zhang Yu, Gao Yu, Guo Gang, Liu Kan, Meng Qingyu, Zhao Chaofei, Wang Dianjun, Song Zhigang, Zhang Xu
Department of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital/Chinese PLA Medical Academy, Beijing, P. R. China.
Department of Pathology, Chinese PLA General Hospital/Chinese PLA Medical Academy, Beijing, P. R. China.
Sci Rep. 2016 Aug 4;6:30886. doi: 10.1038/srep30886.
Targeted drug decisions in metastatic renal cell carcinoma are exclusively made on the basis of clinical criteria. We investigated whether these biomarkers (HIF-1α, HIF-2α, CAIX, VEGF, VEGFR1, VEGFR2, VEGFR3, PDGFB, PDGFRA, PDGFRB, CD31, CD44, bcl-xL, KIT, p21, CXCR4, PTEN, (CSF)-1R, RET, and FLT-3) can predictive the different effects between sunitinib and sorafenib treatments and are available to guide targeted drug selection. We enrolled all patients who underwent nephrectomy with postoperative sunitinib- or sorafenib-treatment at our institution from 2007 to 2012. Immunohistochemical approach was applied to assess the potential differential effects of immunostainings between sunitinib- and sorafenib-treated groups. We found that patients with high HIF-2α, CD31 expression showed greater relative PFS and OS benefit and patients with high CAIX expression presented greater relative OS benefit from sunitinib than from sorafenib, patients with high VEGFR1 or PDGFRB expression levels exhibited worse relative PFS benefit from sunitinib than from sorafenib. Namely high HIF-2α, CD31, and CAIX expression levels along with low VEGFR1 and PDGFRB expression levels improved the benefit of sunitinib treatment compared with sorafenib treatment. These results can identify whether patients can benefit more from sunitinib or sorafenib for drug selection guidance, eventually with precision medicine.
转移性肾细胞癌的靶向药物决策完全基于临床标准。我们研究了这些生物标志物（缺氧诱导因子-1α、缺氧诱导因子-2α、碳酸酐酶IX、血管内皮生长因子、血管内皮生长因子受体1、血管内皮生长因子受体2、血管内皮生长因子受体3、血小板衍生生长因子B、血小板衍生生长因子受体A、血小板衍生生长因子受体B、血小板内皮细胞黏附分子-1、CD44、凋亡抑制蛋白、原癌基因c-KIT、周期蛋白依赖性激酶抑制剂p21、趋化因子受体CXCR4、第10号染色体缺失的磷酸酶及张力蛋白同源物、集落刺激因子-1受体、原癌基因RET、FMS样酪氨酸激酶3）是否能够预测舒尼替尼和索拉非尼治疗的不同效果，并可用于指导靶向药物选择。我们纳入了2007年至2012年在我院接受肾切除术后接受舒尼替尼或索拉非尼治疗的所有患者。采用免疫组织化学方法评估舒尼替尼和索拉非尼治疗组免疫染色的潜在差异效应。我们发现，缺氧诱导因子-2α、血小板内皮细胞黏附分子-1表达高的患者显示出更大的相对无进展生存期和总生存期获益，碳酸酐酶IX表达高的患者从舒尼替尼获得的相对总生存期获益大于索拉非尼，血管内皮生长因子受体1或血小板衍生生长因子受体B表达水平高的患者从舒尼替尼获得的相对无进展生存期获益比索拉非尼差。也就是说，与索拉非尼治疗相比，缺氧诱导因子-2α、血小板内皮细胞黏附分子-1和碳酸酐酶IX高表达水平以及血管内皮生长因子受体1和血小板衍生生长因子受体B低表达水平提高了舒尼替尼治疗的获益。这些结果可以确定患者在药物选择指导方面是从舒尼替尼还是索拉非尼中获益更多，最终实现精准医疗。
