Hofmann Linda, Abou Kors Tsima, Ezić Jasmin, Niesler Beate, Röth Ralph, Ludwig Sonja, Laban Simon, Schuler Patrick J, Hoffmann Thomas K, Brunner Cornelia, Medyany Valentin, Theodoraki Marie-Nicole
Department of Otorhinolaryngology, Head and Neck Surgery, Ulm University Medical Center, Ulm, Germany.
nCounter Core Facility, Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany.
Front Cell Dev Biol. 2022 Aug 22;10:971596. doi: 10.3389/fcell.2022.971596. eCollection 2022.
Head and neck squamous cell carcinomas (HNSCC) lack tumor-specific biomarkers. Exosomes from HNSCC patients carry immunomodulatory molecules, and correlate with clinical parameters. We compared miRNA profiles of plasma- and saliva-derived exosomes to reveal liquid biomarker candidates for HNSCC. Exosomes were isolated by differential ultracentrifugation from corresponding plasma and saliva samples from 11 HNSCC patients and five healthy donors (HD). Exosomal miRNA profiles, as determined by nCounter SPRINT technology, were analyzed regarding their diagnostic and prognostic potential, correlated to clinical data and integrated into network analysis. 119 miRNAs overlapped between plasma- and saliva-derived exosomes of HNSCC patients, from which 29 tumor-exclusive miRNAs, associated with , and signaling, were selected. By intra-correlation of tumor-exclusive miRNAs from plasma and saliva, top 10 miRNA candidates with the strongest correlation emerged as diagnostic panels to discriminate cancer and healthy as well as potentially prognostic panels for disease-free survival (DFS). Further, exosomal miRNAs were differentially represented in human papillomavirus (HPV) positive and negative as well as low and high stage disease. A plasma- and a saliva-derived panel of tumor-exclusive exosomal miRNAs hold great potential as liquid biopsy for discrimination between cancer and healthy as well as HPV status and disease stage. Exosomal miRNAs from both biofluids represent a promising tool for future biomarker studies, emphasizing the possibility to substitute plasma by less-invasive saliva collection.
头颈部鳞状细胞癌（HNSCC）缺乏肿瘤特异性生物标志物。HNSCC患者的外泌体携带免疫调节分子，并与临床参数相关。我们比较了血浆和唾液来源的外泌体的miRNA谱，以揭示HNSCC的液体生物标志物候选物。通过差速超速离心从11例HNSCC患者和5名健康供体（HD）的相应血浆和唾液样本中分离出外泌体。通过nCounter SPRINT技术测定的外泌体miRNA谱，分析其诊断和预后潜力，与临床数据相关并整合到网络分析中。119种miRNA在HNSCC患者的血浆和唾液来源的外泌体之间重叠，从中选择了29种与 、 和 信号传导相关的肿瘤特异性miRNA。通过血浆和唾液中肿瘤特异性miRNA的相互关联，相关性最强的前10种miRNA候选物作为诊断组出现，用于区分癌症和健康状况以及无病生存期（DFS）的潜在预后组。此外，外泌体miRNA在人乳头瘤病毒（HPV）阳性和阴性以及低、高分期疾病中差异表达。一组血浆和唾液来源的肿瘤特异性外泌体miRNA作为液体活检在区分癌症和健康状况以及HPV状态和疾病分期方面具有巨大潜力。来自两种生物流体的外泌体miRNA代表了未来生物标志物研究的一个有前途的工具，强调了用侵入性较小的唾液采集替代血浆的可能性。
