Tumor-derived exosomes (TEXs) are involved in tumor progression and the immune modulation process and mediate intercellular communication in the tumor microenvironment. Although exosomes are considered promising liquid biomarkers for disease diagnosis, it is difficult to discriminate TEXs and to develop TEX-based predictive biomarkers. In this study, the gene expression profiles and clinical information were collected from The Cancer Genome Atlas (TCGA) database, IMvigor210 cohorts, and six independent Gene Expression Omnibus datasets. A TEXs-associated signature named TEXscore was established to predict overall survival in multiple cancer types and in patients undergoing immune checkpoint blockade therapies. Based on exosome-associated genes, we first constructed a tumor-derived exosome signature named TEXscore using a principal component analysis algorithm. In single-cell RNA-sequencing data analysis, ascending TEXscore was associated with disease progression and poor clinical outcomes. In the TCGA Pan-Cancer cohort, TEXscore was elevated in tumor samples rather than in normal tissues, thereby serving as a reliable biomarker to distinguish cancer from non-cancer sources. Moreover, high TEXscore was associated with shorter overall survival across 12 cancer types. TEXscore showed great potential in predicting immunotherapy response in melanoma, urothelial cancer, and renal cancer. The immunosuppressive microenvironment characterized by macrophages, cancer-associated fibroblasts, and myeloid-derived suppressor cells was associated with high TEXscore in the TCGA and immunotherapy cohorts. Besides, TEXscore-associated miRNAs and gene mutations were also identified. Further experimental research will facilitate the extending of TEXscore in tumor-associated exosomes. TEXscore capturing tumor-derived exosome features might be a robust biomarker for prognosis and treatment responses in independent cohorts.

中文翻译：

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肿瘤衍生外泌体特征的单细胞分析与预后和免疫治疗反应相关

肿瘤来源的外泌体（TEXs）参与肿瘤进展和免疫调节过程，并介导肿瘤微环境中的细胞间通讯。尽管外泌体被认为是用于疾病诊断的有前途的液体生物标志物，但很难区分 TEX 并开发基于 TEX 的预测性生物标志物。在本研究中，基因表达谱和临床信息来自癌症基因组图谱 (TCGA) 数据库、IMvigor210 队列和六个独立的基因表达综合数据集。建立了一个名为 TEXscore 的与 TEXs 相关的特征，以预测多种癌症类型和接受免疫检查点阻断治疗的患者的总生存期。基于外泌体相关基因，我们首先使用主成分分析算法构建了一个名为 TEXscore 的肿瘤衍生外泌体特征。在单细胞 RNA 测序数据分析中，升高的 TEXscore 与疾病进展和不良临床结果相关。在 TCGA Pan-Cancer 队列中，TEXscore 在肿瘤样本中升高，而不是在正常组织中，因此可作为区分癌症和非癌症来源的可靠生物标志物。此外，高 TEXscore 与 12 种癌症类型的总生存期较短有关。TEXscore 在预测黑色素瘤、尿路上皮癌和肾癌的免疫治疗反应方面显示出巨大潜力。以巨噬细胞、癌症相关成纤维细胞和髓源性抑制细胞为特征的免疫抑制微环境与 TCGA 和免疫治疗队列中的高 TEXscore 相关。此外，还鉴定了与 TEXscore 相关的 miRNA 和基因突变。进一步的实验研究将促进 TEXscore 在肿瘤相关外泌体中的扩展。TEXscore 捕获肿瘤衍生的外泌体特征可能是独立队列中预后和治疗反应的可靠生物标志物。