PAK1 expression determines poor prognosis and immune evasion in metastatic renal cell carcinoma patients
PAK1 expression determines poor prognosis and immune evasion in metastatic renal cell carcinoma patients
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PAK1表达决定转移性肾细胞癌患者的不良预后和免疫逃避
DOI：
10.1016/j.urolonc.2019.10.010
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发表时间：
2020-04-01
影响因子：
2.7
通讯作者：
Guo, Jianming
中科院分区：
文献类型：
--
作者：
Qu, Yang;Lin, Zhiyuan;Guo, Jianming
背景：先前的研究表明，PAK1的表达在不同肿瘤患者中的预后价值，包括非转移性肾细胞癌。在这项研究中，我们探讨了转移性肾细胞癌(MRCC)患者接受酪氨酸激酶抑制剂(TKIs)治疗后PAK1表达的预后和药物预测价值。材料和方法：我们回顾了2005-2014年间接受TKIs治疗的138例转移性肾癌患者。分析基于111名符合我们纳入标准的患者。该验证集在1998年至2013年期间在北美纳入了来自癌症基因组图谱肾透明细胞癌队列(TCGA KIRC)的538名肾癌患者。结果：PAK1高表达与总生存期(OS)短(P<；0.001)和无进展生存期(PFS)(P=0.008)相关。多变量分析进一步表明，PAK1的表达是OS和PFS的独立预后因素(风险比3.301[95%可信区间2.579-10.899]，P<；0.001)和PFS(风险比3.108[95%可信区间1.795-5.381]，P<；0.001)。亚组分析显示PAK1在Heng危险标准(OS，P=0.004)的中危患者中更为显著。值得注意的是，接受舒尼替尼治疗的患者在低PAK1亚组中的结果有所改善(OS，P=0.002；PFS，P=0.013)。结论：PAK1高表达预示着接受TKI治疗的肾细胞癌患者预后不良。此外，PAK1是TKIs治疗的潜在预测因子。(C)2019 Elsevier Inc.保留所有权利。
Background: Previous studies have shown the prognostic value of PAK1 expression in different tumor patients, including nonmetastatic renal cell carcinoma. In this study, we explored the prognostic and drug predictive value of PAK1 expression in metastatic renal cell carcinoma (mRCC) patients treated with tyrosine kinase inhibitors (TKIs).Materials and Methods: We retrospectively enrolled 138 mRCC patients treated with TKIs from a single institution from 2005 to 2014. Analyses were based on 111 patients who met our inclusion criteria. The validation set enrolled 538 RCC patients from The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma cohort (TCGA KIRC) between 1998 and 2013 in North America. PAK1 expression was assessed by immunohistochemistry (IHC) on tissue microarrays.Results: High PAK1 expression was associated with short overall survival (OS) (P < 0.001) and progression-free survival (PFS) (P = 0.008). Multivariate analyses further indicated that PAK1 expression was an independent prognostic factor for OS (hazard ratio 3.301 [95% confidence interval 2.579-10.899], P < 0.001) and PFS (hazard ratio 3.108 [95% confidence interval 1.795-5.381], P < 0.001). Subgroup analyses suggested that PAK1 was more significant in patients with the intermediate risk group of Heng risk criteria (OS, P = 0.004). Of note, patients treated with Sunitinib showed improved outcome in the low PAK1 subgroup (OS, P = 0.002; PFS, P = 0.013). Finally, relationship was found between PAK1 expression and natural killer cell-mediated cytotoxicity according to gene profile investigation.Conclusions: High PAK1 expression predicted dismal prognosis in mRCC patients treated with TKIs. Besides, PAK1 was a potential predictor for TKIs treatments. (C) 2019 Elsevier Inc. All rights reserved.