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CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
循环 EVs 长 RNA 分型和解卷积可预测 PDAC 的免疫原性特征和临床结局
英文原题：Circulating EVs long RNA-based subtyping and deconvolution enable prediction of immunogenic signatures and clinical outcome for PDAC.
查看英文原题
Circulating EVs long RNA-based subtyping and deconvolution enable prediction of immunogenic signatures and clinical outcome for PDAC.
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中文摘要
识别胰腺导管腺癌（PDAC）临床适用的分子亚型对于改善患者预后至关重要。然而，传统的依赖组织的转录亚型分型策略具有侵入性，不适合常规临床评估。
在本研究中，我们开发了一种基于循环细胞外囊泡（cEV）长RNA（exLR）的PDAC分型方法，并提供了源自exLR的特征用于预测PDAC的免疫原性特征和临床结局。
我们纳入了426例个体，其中227例PDAC作为内部队列，来自另外两个医疗中心的118例PDAC作为独立验证队列，81例健康个体作为对照。对所有血浆样本进行了exLR测序。
我们发现，基于血浆exLR谱，PDAC可分为三种亚型。每个亚群均显示出其自身的分子特征，并与患者临床预后相关。免疫细胞来源的cEV比例在PDAC亚型之间发生变化，并与癌组织中的TIL（肿瘤浸润淋巴细胞）相互关联。
此外，我们发现组织和血液EV之间的免疫调节因子具有显著一致性，并获得了潜在的PDAC治疗靶点。最重要的是，我们构建了一个由九个exLR衍生的、可应用于组织的特征标签，用于PDAC的预后评估。基于循环exLR的特征可能为多种类型癌症的个体化治疗和预测患者结局提供一个有吸引力的平台。
展开英文摘要原文
Identification of clinically applicable molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) is crucial to improving patient outcomes.
However, the traditional tissue-dependent transcriptional subtyping strategies are invasive and not amenable to routine clinical evaluation. In this study, we developed a circulating extracellular vesicle (cEV) long RNA (exLR)-based PDAC subtyping method and provided exLR-derived signatures for predicting immunogenic features and clinical outcomes in PDAC.
We enrolled 426 individuals, among which 227 PDACs served as an internal cohort, 118 PDACs from two other medical centers served as an independent validation cohort, and 81 healthy individuals served as the control. ExLR sequencing was performed on all plasma samples.
We found that PDAC could be categorized into three subtypes based on plasma exLR profiles. Each subpopulation showed its own molecular features and was associated with patient clinical prognosis. The immunocyte-derived cEV fractions were altered among PDAC subtypes and interconnected with tumor-infiltrating lymphocytes in cancerous tissue.
Additionally, we found a significant concordance of immunoregulators between tissue and blood EVs, and we harvested potential PDAC therapeutic targets. Most importantly, we constructed a nine exLR-derived, tissue-applicable signature for prognostic assessment of PDAC. The circulating exLR-based features may offer an attractive platform for personalized treatment and predicting patient outcomes in multiple types of cancer.
论文信息
- 作者
- Li Y、Li Y、Yu S、Qian L、Chen K、Lai H、Zhang H、Li Y
- 单位
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, and the Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, 270 Dong An Road, Shanghai 200032, China.China
- 期刊
- Molecular therapy. Nucleic acids2021 Dec 3
- 原文标识
- PubMed 34631279 · DOI 10.1016/j.omtn.2021.08.017
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