Gao Guanghui, Zhang Xiao-Dong, Qu Hu, Yao Bing, Zhou Yuxi, Xiang Jianxing, Chen Chunxiang, Hou Ting, Chen Kai, Xu Junying
Department of Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.
Department of Medical Oncology, Affiliated Tumor Hospital of Nantong University, Nantong, China.
Ann Transl Med. 2021 Apr;9(8):677. doi: 10.21037/atm-21-853.
Immune checkpoint inhibitors blocking programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) have emerged as effective treatment options for cancer. However, immunotherapy is only effective in a subset of patients. Identifying effective biomarkers to predict the treatment response to PD-1/PD-L1 inhibitors remains an unmet clinical need.
This study retrospectively analyzed clinical information and genetic profiling results of 16,013 samples from Chinese patients with various cancer types in order to investigate the prevalence of (also known as PD-L1) amplification in various cancer types and its association with existing PD-1/PD-L1 biomarkers, including tumor mutational burden (TMB), microsatellite instability (MSI), and PD-L1 expression.
Amplification of was identified in 174 samples with an overall prevalence of 1.09% among all cancer types in the cohort. The prevalence of amplification in different cancer types and histological subtypes of lung cancer was varied, with cervical cancer having the highest prevalence. Distinct distributions of TMB, MSI, and PD-L1 expression between amplified and wild-type samples were observed in several cancer types as well as among different histological subtypes of lung cancer.
Although amplification was only observed in a small proportion of patients, it demonstrated an association with TMB, MSI, and PD-L1 expression in several common cancer types. The molecular features of in different cancer types are heterogeneous. The role of amplification as a novel biomarker of PD-1/PD-L1 inhibitors remains to be characterized in future prospective clinical studies.
阻断程序性细胞死亡蛋白1（PD-1）或程序性细胞死亡配体1（PD-L1）的免疫检查点抑制剂已成为癌症的有效治疗选择。然而，免疫疗法仅对一部分患者有效。识别有效的生物标志物以预测对PD-1/PD-L1抑制剂的治疗反应仍然是一项未满足的临床需求。
本研究回顾性分析了来自中国不同癌症类型患者的16013份样本的临床信息和基因谱分析结果，以调查（也称为PD-L1）扩增在不同癌症类型中的发生率及其与现有PD-1/PD-L1生物标志物的关联，包括肿瘤突变负荷（TMB）、微卫星不稳定性（MSI）和PD-L1表达。
在174份样本中鉴定出扩增，在该队列的所有癌症类型中总体发生率为1.09%。肺癌不同癌症类型和组织学亚型中的扩增发生率各不相同，宫颈癌的发生率最高。在几种癌症类型以及肺癌的不同组织学亚型中，观察到扩增样本和野生型样本之间TMB、MSI和PD-L1表达的不同分布。
尽管仅在一小部分患者中观察到扩增，但它在几种常见癌症类型中显示出与TMB、MSI和PD-L1表达有关联。不同癌症类型中的分子特征是异质性的。扩增作为PD-1/PD-L1抑制剂的新型生物标志物的作用仍有待在未来的前瞻性临床研究中加以表征。
