Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Department of Urology, Keio University School of Medicine, Tokyo, Japan.
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Eur Urol. 2022 Feb;81(2):145-148. doi: 10.1016/j.eururo.2021.09.024. Epub 2021 Oct 6.
Immune checkpoint inhibitors (ICIs) have become key agents in the management of clear cell renal cell carcinoma (ccRCC), but their benefits are limited and responders remain unidentified. We investigated the significance of PARP1 in ccRCC using RNA sequencing data for 311 tumors from patients enrolled in prospective clinical trials of PD-1 blockade. Among patients treated with nivolumab (n = 181), overall survival (OS) was significantly higher in the PARP1-low group than in the PARP1-high group (p = 0.006), and PARP1 status was significantly associated with OS (hazard ratio [HR] 1.7; p = 0.007). By contrast, for patients treated with everolimus (n = 130) there was no significant difference by PARP1 status for progression-free survival (PFS; p = 0.9) or OS (p = 0.38). In subgroup analysis for PBRM1-mutated ccRCC, PFS (p = 0.016) and OS (p = 0.004) were significantly longer in the group with PARP1-low status and PBRM1 mutation in comparison to the other groups. In addition, PARP1 status was significantly associated with PFS (HR 2.6; p = 0.007) and OS (HR 3.5; p = 0.016) among patients with PBRM1-mutated ccRCC treated with nivolumab. Our study suggests that PARP1 can be used as a biomarker for predicting response to ICI treatment for patients with PBRM1-mutated ccRCC. PATIENT SUMMARY: Immune checkpoint inhibitors (ICIs) are key agents in the treatment of multiple cancers. We found that expression of the PARP1 protein was associated with survival after ICI treatment and with the response to ICI treatment in patients with clear cell kidney cancer who have a mutation of the PBRM1 gene.
免疫检查点抑制剂（ICIs）已成为治疗透明细胞肾细胞癌（ccRCC）的关键药物，但它们的疗效有限，且应答者仍未确定。我们使用来自前瞻性 PD-1 阻断临床试验的 311 例患者的 RNA 测序数据研究了 PARP1 在 ccRCC 中的意义。在接受nivolumab（n = 181）治疗的患者中，PARP1 低表达组的总生存期（OS）显著高于 PARP1 高表达组（p = 0.006），且 PARP1 状态与 OS 显著相关（风险比[HR] 1.7；p = 0.007）。相比之下，对于接受 everolimus（n = 130）治疗的患者，PARP1 状态对无进展生存期（PFS；p = 0.9）或 OS（p = 0.38）无显著影响。在 PBRM1 突变 ccRCC 的亚组分析中，PARP1 低表达且 PBRM1 突变的患者的 PFS（p = 0.016）和 OS（p = 0.004）显著长于其他组。此外，在接受 nivolumab 治疗的 PBRM1 突变 ccRCC 患者中，PARP1 状态与 PFS（HR 2.6；p = 0.007）和 OS（HR 3.5；p = 0.016）显著相关。我们的研究表明，PARP1 可作为预测 PBRM1 突变 ccRCC 患者对 ICI 治疗反应的生物标志物。
免疫检查点抑制剂（ICIs）是多种癌症治疗的关键药物。我们发现，PARP1 蛋白的表达与接受 ICI 治疗后的生存有关，也与接受 ICI 治疗的 PBRM1 基因突变的透明细胞肾癌患者的反应有关。
