循环细胞外囊泡circ_PPAPDC1A在非小细胞肺癌免疫检查点抑制剂耐药中的诊断和预后作用
Diagnostic and prognostic roles of circulating EVs circ_PPAPDC1A in ICIs resistance in NSCLC.
作者信息
Zou Fang-Wen, Tang Yi-Fang, Zhang Lei-Yi, Xu Shun, Yang Shi-Ze, Li Wen-Ya, Liu Zheng-Hua
机构信息
Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, PR China.
Department of Anesthesiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, PR China.
出版信息
NPJ Precis Oncol. 2025 Sep 18;9(1):316. doi: 10.1038/s41698-025-01102-5.
ICIs resistance presents a significant challenge in clinical practice. Circulating extracellular vesicles circRNAs are promising biomarkers for cancer diagnosis and treatment. This study aimed to determine the oncogenic role of circulating extracellular vesicles circ_PPAPDC1A in ICIs resistance diagnosis and prognostic analysis of NSCLC. We used a co-culture system of NSCLC cells and T cells, and a mice xenograft assay, to evaluate the effect of circ_PPAPDC1A on anti-PD-1 antitumor activity. A multicenter cohort study of 40 patients analyzed the associations between extracellular vesicles circ_PPAPDC1A and ICIs resistance. In vitro, circ_PPAPDC1A reduced the sensitivity of NSCLC cells to ICIs by promoting proliferation and inhibiting apoptosis. In vivo, circ_PPAPDC1A promoted NSCLC progression and induced CD8 T-cell exhaustion. Clinical samples showed circ_PPAPDC1A upregulation in NSCLC patients with ICIs resistance, high diagnostic efficiency (AUC = 0.98), and higher expression associated with shorter PFS. Circulating extracellular vesicles circ_PPAPDC1A may serve as a predictive biomarker for ICIs resistance diagnosis and prognostic analysis.
免疫检查点抑制剂（ICIs）耐药性在临床实践中构成了重大挑战。循环细胞外囊泡circRNAs是癌症诊断和治疗中有前景的生物标志物。本研究旨在确定循环细胞外囊泡circ_PPAPDC1A在非小细胞肺癌（NSCLC）的ICIs耐药性诊断和预后分析中的致癌作用。我们使用NSCLC细胞与T细胞的共培养系统以及小鼠异种移植试验，来评估circ_PPAPDC1A对抗PD-1抗肿瘤活性的影响。一项对40例患者的多中心队列研究分析了细胞外囊泡circ_PPAPDC1A与ICIs耐药性之间的关联。在体外，circ_PPAPDC1A通过促进增殖和抑制凋亡降低了NSCLC细胞对ICIs的敏感性。在体内，circ_PPAPDC1A促进了NSCLC进展并诱导CD8 T细胞耗竭。临床样本显示，circ_PPAPDC1A在具有ICIs耐药性的NSCLC患者中上调，诊断效率高（AUC = 0.98），且其高表达与较短的无进展生存期相关。循环细胞外囊泡circ_PPAPDC1A可作为ICIs耐药性诊断和预后分析的预测生物标志物。
Zotero 插件