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.

中文翻译：

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PARP1作为预测PBRM1突变透明细胞肾细胞癌患者对PD-L1阻断反应的生物标志物的意义

免疫检查点抑制剂 (ICI) 已成为治疗透明细胞肾细胞癌 (ccRCC) 的关键药物，但它们的益处有限，且应答者仍未确定。我们使用来自参加 PD-1 阻断前瞻性临床试验的患者的 311 例肿瘤的 RNA 测序数据研究了 PARP1 在 ccRCC 中的重要性。在接受纳武利尤单抗治疗的患者（n  = 181）中，PARP1 低组的总生存期（OS）显着高于 PARP1 高组（p  = 0.006），PARP1 状态与 OS 显着相关（风险比 [ HR] 1.7；p  = 0.007)。相比之下，对于接受依维莫司治疗的患者（n= 130) PARP1 状态对无进展生存期 (PFS; p  = 0.9) 或 OS ( p  = 0.38) 没有显着差异。在PBRM1突变的 ccRCC 的亚组分析中，与其他组相比， 具有 PARP1 低状态和PBRM1突变的组的PFS ( p  = 0.016) 和 OS ( p = 0.004) 显着更长。此外，在接受纳武单抗治疗的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）显着相关。我们的研究表明，PARP1 可用作预测患有 ICI 治疗的患者对 ICI 治疗反应的生物标志物。PBRM1-突变的ccRCC。

患者总结

免疫检查点抑制剂 (ICI) 是治疗多种癌症的关键药物。我们发现 PARP1 蛋白的表达与 ICI 治疗后的存活率以及具有PBRM1基因突变的透明细胞肾癌患者对 ICI 治疗的反应相关。