Purpose: Given the emergence of PSMA-targeted diagnostic agents and therapeutics, we sought to investigate patterns ofFOLH1expression in RCC and their impacts on RCC outcomes. Methods: We conducted a pooled multi-institutional analysis of patients with RCC having undergone DNA and RNA next-generation sequencing.FOLH1-high/low expression was defined as the ≥75th/<25th percentile of RNA transcripts per million (TPM). Angiogenic, T-effector, and myeloid expression signatures were calculated using previously defined gene sets. Kaplan–Meier estimates were calculated from the time of tissue collection or therapy start. Results: We included 1,724 patients in the analysis. FOLH1 expression was significantly higher in clear cell (71%) compared to non-clear cell RCC tumors (19.0 versus 3.3 TPM,p< 0.001) and varied by specimen site (45% primary kidney/55% metastasis, 13.6 versus 9.9 TPM,p< 0.001).FOLH1expression was correlated with angiogenic gene expression (Spearman = 0.76,p< 0.001) and endothelial cell abundance (Spearman = 0.76,p< 0.001). While OS was similar in patients withFOLH1-high versus -low ccRCC, patients withFOLH1-high clear cell tumors experienced a longer time on cabozantinib treatment (9.7 versus 4.6 months, respectively, HR 0.57, 95% CI 0.35–0.93,p< 0.05). Conclusions: We observed differential patterns ofFOLH1expression based on histology and tumor site in RCC.FOLH1was correlated with angiogenic gene expression, increased OS, and a longer duration of cabozantinib treatment.
目的：鉴于PSMA靶向诊断剂和治疗药物的出现，本研究旨在探讨肾细胞癌（RCC）中FOLH1的表达模式及其对RCC预后的影响。方法：我们对接受DNA和RNA二代测序的RCC患者进行了多机构汇总分析。FOLH1高/低表达定义为每百万RNA转录本（TPM）≥75百分位数/<25百分位数。使用先前定义的基因集计算血管生成、T细胞效应和髓系细胞表达特征。从组织采集或治疗开始时间计算Kaplan-Meier估计值。结果：分析共纳入1,724例患者。与透明细胞RCC（71%）相比，非透明细胞RCC肿瘤中FOLH1表达显著更高（19.0 TPM对3.3 TPM，p<0.001），且表达水平因标本部位而异（45%原发肾脏/55%转移灶，13.6 TPM对9.9 TPM，p<0.001）。FOLH1表达与血管生成基因表达（Spearman=0.76，p<0.001）及内皮细胞丰度（Spearman=0.76，p<0.001）呈正相关。虽然FOLH1高表达与低表达透明细胞RCC患者的总生存期相似，但FOLH1高表达透明细胞肿瘤患者接受卡博替尼治疗的时间更长（分别为9.7个月对4.6个月，HR 0.57，95% CI 0.35–0.93，p<0.05）。结论：我们观察到RCC中FOLH1表达模式因组织学类型和肿瘤部位存在差异。FOLH1表达与血管生成基因表达、总生存期延长及卡博替尼治疗持续时间增加相关。
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