血浆外囊泡长RNA分析鉴定了肺鳞状细胞癌的免疫化学疗法功效的预测性特征
Plasma extracellular vesicle long RNA profiling identifies a predictive signature for immunochemotherapy efficacy in lung squamous cell carcinoma
影响因子:5.90000
分区:医学2区 / 免疫学2区
发表日期:2024
作者:
Xin Zhang, Jiatao Liao, Wenyue Yang, Qiaojuan Li, Zhen Wang, Hui Yu, Xianghua Wu, Huijie Wang, Si Sun, Xinmin Zhao, Zhihuang Hu, Jialei Wang
摘要
免疫检查点抑制剂（ICI）的引入标志着治疗肺鳞状细胞癌（LUSC）的范式转移，强调迫切需要精确的分子生物标志物可靠地预测治疗疗效。这项研究旨在通过关注血浆外囊泡（EV）衍生的长RNA（EXLRS）来鉴定免疫化学疗法疗效的潜在生物标志物。我们招募了78名接受一线免疫化学疗法的高级LUSC患者。收集血浆样品，并进行EXLR测序以建立基线谱。对42名患者进行了回顾性分析，以鉴定差异表达的EXLR。使用定量逆转录PCR（QRT-PCR）对顶部差异表达的EXLR进行进一步验证。使用单变量COX分析来确定这些EXLR的预后意义。基于这些发现，我们开发了一个预测性签名（p-签名）。在对42名患者的回顾性分析中，我们确定了460个差异表达的EXLR，其途径与白细胞迁移有关，在非反应者之间特别富集。单变量COX分析显示45个具有预后意义的EXLR。使用QRT-PCR，将CXCL8，SSH3和SDHAF1验证为响应者和非反应者之间差异表达的前6个蛋白质编码EXLR验证。包括这三个EXLR组成的p签名在区分反应者和非反应者方面表现出很高的精度，在回顾性队列中，曲线下的面积为0.904，而预期的同类群中的曲线为0.812。这项研究很高的是，这项研究凸显了血浆EXLR exlr exlr Periles在预测LUSC治疗效果方面的可能性。有趣的是，较低的p签名分数与活化的CD4+和CD8+ T细胞的丰度增加有关，表明具有更健壮的免疫环境。这些发现表明，P-Signature可以作为指导LUSC的个性化和有效治疗策略的宝贵工具。
Abstract
The introduction of Immune Checkpoint Inhibitors (ICIs) has marked a paradigm shift in treating Lung Squamous Cell Carcinoma (LUSC), emphasizing the urgent need for precise molecular biomarkers to reliably forecast therapeutic efficacy. This study aims to identify potential biomarkers for immunochemotherapy efficacy by focusing on plasma extracellular vesicle (EV)-derived long RNAs (exLRs).We enrolled 78 advanced LUSC patients undergoing first-line immunochemotherapy. Plasma samples were collected, and exLR sequencing was conducted to establish baseline profiles. A retrospective analysis was performed on 42 patients to identify differentially expressed exLRs. Further validation of the top differentially expressed exLRs was conducted using quantitative reverse transcription PCR (qRT-PCR). Univariate Cox analysis was applied to determine the prognostic significance of these exLRs. Based on these findings, we developed a predictive signature (p-Signature).In the retrospective analysis of 42 patients, we identified 460 differentially expressed exLRs, with pathways related to leukocyte migration notably enriched among non-responders. Univariate Cox analysis revealed 45 exLRs with prognostic significance. The top 6 protein-coding exLRs were validated using qRT-PCR, identifying CXCL8, SSH3, and SDHAF1 as differentially expressed between responders and non-responders. The p-Signature, comprising these three exLRs, demonstrated high accuracy in distinguishing responders from non-responders, with an Area Under the Curve (AUC) of 0.904 in the retrospective cohort and 0.812 in the prospective cohort.This study highlighted the potential of plasma exLR profiles in predicting LUSC treatment efficacy. Intriguingly, lower p-Signature scores were associated with increased abundance of activated CD4+ and CD8+ T cells, indicating a more robust immune environment. These findings suggest that the p-Signature could serve as a valuable tool in guiding personalized and effective therapeutic strategies for LUSC.