Background: Biomarkers for HNSCC are still lacking. Biomolecules obtained via liquid biopsy are being investigated for diagnosis, prognosis, and therapy monitoring, including extracellular vesicles (EVs) and EV-cargo, e.g., proteins, RNA, and microRNA. This study aims to understand localization-dependent EV-microRNA expression in blood sera, their dynamics over time (12 months FU), and insights into their potential in diagnostics and therapy monitoring. Methods: Via liquid biopsy, blood serum was taken from 50 patients with HNSCC and 16 controls. Extracellular vesicles were isolated from serum by precipitation, and the contained microRNA-21, -1246, -200c, -let-7a, -181a, and -26a were amplified by reverse transcription and determined with real-time PCR. Expression ratios (HNSCC to healthy controls) were collated with the patients’ clinical parameters. A second liquid biopsy was carried out avg. 12 months later in the tumor aftercare. A sub-analysis with the Oropharynx subsite was implemented. Results: EV-mir-21, -let-7a, and -181a were 2.5–3-fold higher expressed in HPV/p16+ than in HPV/p16- HNSCC. Different expressions of EV-mir-181a and -26a could be demonstrated depending on the therapy modality. Conclusions: EV-microRNA could be a promising biomarker in the diagnosis and therapy monitoring of HNSCC. A systematic comparison of EV- and tissue microRNA expression in different HNSCC-subsites is needed.
背景:目前仍缺乏针对头颈部鳞状细胞癌(HNSCC)的有效生物标志物。通过液体活检获取的生物分子,包括细胞外囊泡(EVs)及其携带的蛋白质、RNA和微小RNA等成分,正被用于诊断、预后评估和治疗监测的研究。本研究旨在探究血液中EV-微小RNA的表达与肿瘤部位的相关性,分析其随时间(12个月随访期)的动态变化,并评估其在诊断和治疗监测中的潜在价值。方法:通过液体活检采集50例HNSCC患者和16例对照者的血清样本。采用沉淀法分离血清中的细胞外囊泡,通过逆转录扩增囊泡内包含的微小RNA-21、-1246、-200c、-let-7a、-181a和-26a,并利用实时荧光定量PCR进行检测。将表达比值(HNSCC患者与健康对照者)与患者临床参数进行关联分析。在平均12个月后的肿瘤康复期进行第二次液体活检。针对口咽亚部位进行了亚组分析。结果:在HPV/p16阳性HNSCC患者中,EV-mir-21、-let-7a和-181a的表达水平较HPV/p16阴性患者高出2.5-3倍。EV-mir-181a和-26a的表达差异与治疗方式相关。结论:EV-微小RNA有望成为HNSCC诊断和治疗监测的潜在生物标志物。未来需要对不同HNSCC亚部位中EV与组织微小RNA的表达进行系统比较。