Immune Biomarkers in Metastatic Castration-resistant Prostate Cancer
Immune Biomarkers in Metastatic Castration-resistant Prostate Cancer
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DOI：
10.1016/j.euo.2022.04.004
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发表时间：
2022-12-12
影响因子：
8.2
通讯作者：
Bono, Johann S. de
中科院分区：
文献类型：
--
作者：
de la Maza, Maria Dolores Fenor;Chandran, Khobe;Bono, Johann S. de
背景资料：转移性去势抵抗性前列腺癌（mCRPC）是一种异质性疾病，需要进行分子分层以改善临床结局。预测性生物标志物的鉴定可能对这些患者的护理产生重大影响，但在这种情况下用于研究的转移组织样本的可用性是有限的。目的：研究对mCRPC免疫治疗具有潜在临床实用性的免疫生物标志物的患病率，并确定其与总生存期（OS）的相关性。设计、设置和参与者：通过全外显子组测序、靶向下一代测序、RNA测序、肿瘤突变负荷、T细胞炎症基因表达谱，（TcellinfGEP）评分（Nanostring），和程序性细胞死亡1配体1（PD-L1），共济失调-毛细血管扩张突变（ATM），磷酸酶和张力蛋白同源物（PTEN）、SRY同源盒2（SOX 2）和神经内分泌特征的存在。结果测量和统计分析：phi系数确定感兴趣的生物标志物之间的相关性。采用Kaplan-Meier曲线和考克斯回归分析校正的风险比（aHR）评估OS。结果和局限性：免疫组化检测PD-L1和SOX 2蛋白表达（分别为合并阳性评分>= 1和>5%细胞），分别为24例（33%）和27例（27%）mCRPC活检; 23例（26%）mCRPC活检具有高TcellinfGEP评分（>-0.318）。PD-L1蛋白表达与TcellinfGEP评分呈正相关（phi 0.63 [0.45; 0.76]）。PD-L1蛋白表达（aHR：1.90 [1.05; 3.45]）、高TcellinfGEP评分（aHR：1.86 [1.04; 3.31]）和SOX 2表达（aHR：2.09 [1.20; 3.64]）与OS较差相关。结论：PD-L1、TcellinfGEP评分和SOX 2是mCRPC结局的预后指标。如果得到验证，纳入生存终点的预测性生物标志物研究需要考虑这些发现。
Background: Metastatic castration-resistant prostate cancer (mCRPC) is a heteroge-neous disease in which molecular stratification is needed to improve clinical outcomes. The identification of predictive biomarkers can have a major impact on the care of these patients, but the availability of metastatic tissue samples for research in this setting is limited.Objective: To study the prevalence of immune biomarkers of potential clinical utility to immunotherapy in mCRPC and to determine their association with overall survival (OS).Design, setting, and participants: From 100 patients, mCRPC biopsies were assayed by whole exome sequencing, targeted next-generation sequencing, RNA sequencing, tumor mutational burden, T-cell-inflamed gene expression profile (TcellinfGEP) score (Nanostring), and immunohistochemistry for programmed cell death 1 ligand 1 (PD -L1), ataxia-telangiectasia mutated (ATM), phosphatase and tensin homolog (PTEN), SRY homology box 2 (SOX2), and the presence of neuroendocrine features.Outcome measurements and statistical analysis: The phi coefficient determined correla-tions between biomarkers of interest. OS was assessed using Kaplan-Meier curves and adjusted hazard ratios (aHRs) from Cox regression.Results and limitations: PD-L1 and SOX2 protein expression was detected by immuno-histochemistry (combined positive score >= 1 and >5% cells, respectively) in 24 (33%) and 27 (27%) mCRPC biopsies, respectively; 23 (26%) mCRPC biopsies had high TcellinfGEP scores (>-0.318). PD-L1 protein expression and TcellinfGEP scores were positively corre-lated (phi 0.63 [0.45; 0.76]). PD-L1 protein expression (aHR: 1.90 [1.05; 3.45]), high TcellinfGEP score (aHR: 1.86 [1.04; 3.31]), and SOX2 expression (aHR: 2.09 [1.20; 3.64]) were associated with worse OS.Conclusions: PD-L1, TcellinfGEP score, and SOX2 are prognostic of outcome from the mCRPC setting. If validated, predictive biomarker studies incorporating survival end-points need to take these findings into consideration.