Exosomes containing microRNAs (miRNAs) might have utility as biomarkers to predict the risk of treatment failure in extranodal NK/T-cell lymphoma (ENKTL) because exosomal cargo miRNAs could reflect tumor aggressiveness. We analyzed the exosomal miRNAs of patients in favorable (n = 22) and poor outcome (n = 23) groups in a training cohort. Then, using the Nanostring nCounter® microRNA array, we compared them with miRNAs identified in human NK/T lymphoma (NKTL) cell line-derived exosomes to develop exosomal miRNA profiles. We validated the prognostic value of serum exosomal miRNA profiles with an independent cohort (n = 85) and analyzed their association with treatment resistance using etoposide-resistant cell lines. A comparison of the top 20 upregulated miRNAs in the training cohort with poor outcomes with 16 miRNAs that were upregulated in both NKTL cell lines, identified five candidate miRNAs (miR-320e, miR-4454, miR-222-3p, miR-21-5p, and miR-25-3p). Among these, increased levels of exosomal miR-4454, miR-21-5p, and miR-320e were associated with poor overall survival in the validation cohort. Increased levels were also found in relapsed patients post-treatment. These three miRNAs were overexpressed in NKTL cell lines that were resistant to etoposide. Furthermore, transfection of NKTL cell lines with miR-21-5p and miR-320e induced an increase in expression of the proinflammatory cytokines such as macrophage inflammatory protein 1 alpha. These studies show that serum levels of exosomal miR-21-5p, miR-320e, and miR-4454 are increased in ENKTL patients with poor prognosis. Upregulation of these exosomal miRNAs in treatment-resistant cell lines suggests they have a role as biomarkers for the identification of ENKTL patients at high risk of treatment failure.Keywords:NK/T-cell lymphoma; biomarker; exosome; microRNA cancer.

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乐备实（上海优宁维生物科技股份有限公司旗下全资子公司），是国内专注于提供高质量蛋白检测以及组学分析服务的实验服务专家，自2018年成立以来，乐备实不断寻求突破，公司的服务技术平台已扩展到单细胞测序、空间多组学、流式检测、超敏电化学发光、Luminex多因子检测、抗体芯片、PCR Array、ELISA、Elispot、PLA蛋白互作、多色免疫组化、DSP空间多组学等30多个，建立起了一套涵盖基因、蛋白、细胞以及组织水平实验的完整检测体系。

 
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