PTEN 参与肾细胞癌对舒尼替尼和索拉非尼的耐药。
PTEN Is Involved in Sunitinib and Sorafenib Resistance in Renal Cell Carcinoma.
机构信息
Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
出版信息
Anticancer Res. 2020 Apr;40(4):1943-1951. doi: 10.21873/anticanres.14149.
BACKGROUND/AIM: Targeted receptor tyrosine kinase inhibitor (TKI) is a standard treatment in advanced renal cell carcinoma (RCC). However, the role of PTEN in TKI resistance remains poorly understood. We aimed to determine the functional role of PTEN knockout and analyse the predictive significance of PTEN expression for TKI treatment in RCC.
MATERIALS AND METHODS
We developed PTEN knockout cells in RCC cell lines using the CRISPR-Cas9 system and analysed the effect of PTEN knockout on spheroid formation and resistance to sunitinib and sorafenib.
RESULTS
PTEN knockout promoted spheroid formation and decreased sunitinib/sorafenib sensitivity in RCC cell lines. PTEN immunohistochemistry in 74 metastatic RCCs treated with sunitinib and sorafenib revealed negative PTEN expression in 23% of samples. Kaplan-Meier analysis showed a significant association of negative PTEN expression with poor progression-free survival in metastatic RCC treated with sunitinib and sorafenib (p=0.024) or sunitinib alone (p=0.009).
CONCLUSION
PTEN may be a biomarker and therapeutic target in patients with metastatic RCC.
背景/目的：针对受体酪氨酸激酶抑制剂（TKI）是晚期肾细胞癌（RCC）的标准治疗方法。然而，PTEN 在 TKI 耐药中的作用仍知之甚少。我们旨在确定 PTEN 敲除的功能作用，并分析 PTEN 表达对 RCC 中 TKI 治疗的预测意义。
材料和方法
我们使用 CRISPR-Cas9 系统在 RCC 细胞系中开发了 PTEN 敲除细胞，并分析了 PTEN 敲除对球体形成和对舒尼替尼和索拉非尼耐药性的影响。
结果
PTEN 敲除促进了 RCC 细胞系中球体的形成，并降低了舒尼替尼/索拉非尼的敏感性。对接受舒尼替尼和索拉非尼治疗的 74 例转移性 RCC 的 74 例进行了 PTEN 免疫组化分析，结果显示 23%的样本中存在 PTEN 表达阴性。Kaplan-Meier 分析显示，在接受舒尼替尼和索拉非尼（p=0.024）或舒尼替尼单独治疗的转移性 RCC 患者中，PTEN 表达阴性与无进展生存期差显著相关（p=0.009）。
结论
PTEN 可能是转移性 RCC 患者的生物标志物和治疗靶点。
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